NeuroAnatomy Flashcards
Meningiocele
A meningocele is a birth defect where there is a sac protruding from the spinal column. The sac includes spinal fluid, but does not contain neural tissue. It may be covered with skin or with meninges (the membranes that cover the central nervous system).
Meningocele vs myelomeningocele?
In meningocele, the sac may be covered by a thin layer of skin. In most cases of myelomeningocele, there is no layer of skin covering the sac and an area of abnormally developed spinal cord tissue is usually exposed.
rabies symptoms
emotional, hippocampus - 3 weeks after bite, bouts of terror and rage
how travel?
fast retrograde transport,
Several weeks later, he developed profound changes in his emotional state and suffered from bouts of terror and rage. A clinician who examined the young man suspected that the raccoon that bit him was rabid, and the rabies virus had affected his hippocampus.
different types of neurons
pseudoneurons
sense blood pressure changes - vagus(nodose) and glossophyngieal ganglia -
Pseudo-unipolar neurons in the nodose ganglion sense systemic blood pressure changes
and
Dorsal root ganglia
pseudo-unipolar neurons, a single axon arising from the cell body divides into two branches. One of the branches terminates as fine endings that serve as peripheral receptors, whereas the other branch terminates on neurons in the central nervous system (CNS).
The peripheral nerve endings of the pseudo-unipolar neurons located in the nodose (vagus nerves) and petrosal (glossopharyngeal nerves) ganglia terminate in the vascular walls of the carotid sinus and aortic arch and sense blood pressure changes. Signals received from the vascular nerve endings are transmitted to the CNS for making appropriate adjustment in the systemic blood pressure.
Other pseudo-unipolar neurons lie in the dorsal root ganglia.
Golgi neurons, multipolar?
Golgi 1 - long axon
Golgi 2 - short
A Golgi I (or Golgi type I) neuron is a neuron which has a long axon that begins in the grey matter of the central nervous system and may extend from there. It is also known as a projection neuron. They include the neurons forming peripheral nerves and long tracts of brain and spinal cord.
Golgi type I neurons have relatively long axons, whereas Golgi type II neurons have relatively short axons.
Multipolar neurons (e.g., motor neurons in the anterior horn of the spinal cord) have several dendrites and one long axon arising from the cell body.
grey matter in brain?
inside or outside?
Grey matter is mainly located on the surface of the brain - white matter buried deep. The spinal cord is arranged in the opposite way, with grey matter found deep inside its core and the insulating white matter wrapped around the outside.
Grey matter contains most of the brain’s neuronal cell bodies. The grey matter includes regions of the brain involved in muscle control, and sensory perception such as seeing and hearing, memory, emotions, speech, decision making, and self-control.
axon hillock
no Nissl - therefore -no protein synthesis
Nissl substance consists of RNA
Nissl material, is a large granular body found in body of neurons. These granules are of rough endoplasmic reticulum (RER) with rosettes of free ribosomes, and are the site of protein synthesis.
The axon hillock is located at the end of the soma and controls the firing of the neuron. If the total strength of the signal exceeds the threshold limit of the axon hillock, the structure will fire a signal (known as an action potential) down the axon.
axon hillock special properties?
portion of the soma from which the axon arises
The axon hillock and initial segment have a number of specialized properties that make them capable of action potential generation, including adjacency to the axon and a much higher density of voltage-gated ion channels than is found in the rest of the cell body.
cut arm - what happens?
Small, angulated muscle fibers
denervation atrophy of skeletal muscle appears as small muscle fibers with decreased cross-sectional area, which are angulated or triangular and arranged in small groups
After transection of a peripheral nerve, degeneration of the distal nerve section begins almost immediately. Wallerian degeneration (also called anterograde degeneration) refers specifically to the process whereby nerve fibers (generally the axon) distal to the site of transection undergo swelling, appear irregularly shaped, and lose their myelin (as depicted in image A). This is due to the loss of connection with the soma, which is the source of metabolic nourishment. Retrograde degeneration, proximal to the axonal injury, results in peripheral displacement of the nucleus, dissolution of Nissl bodies, and enlargement of the cell body. This is known as the axonal reaction, or chromatolysis.
can nerve regeneration occur in PNS? CNS?
PNS only
Degenerative myocytes ?
Gower sign (a pattern of using upper extremities to rise from the ground r
duchenne’s
with interstitial fibrofatty infiltrate corresponds to Duchenne muscular dystrophy (DMD), an X-linked muscular dystrophy that is often associated with Gower sign (a pattern of using upper extremities to rise from the ground rather than lower extremities) and pseudohypertrophy of the calves.
“ragged-red” fibers in disarray with mitochondrial changes, some described as “parking-lot” inclusions because of crystalline deposits seen intracellularly.
Mitochondrial myopathies are debilitating and often lethal conditions that manifest with weakness and other syndromic abnormalities, based on the underlying pathologic changes.
polymyositis, dermatomyositis.
Transfascicular and intracellular CD8+ mediated inflammation corresponds to polymyositis, an autoimmune condition with features similar to dermatomyositis. Endomysial inflammation involving CD8+ T-lymphocytes can be seen on histologic examination.
chromatolysis?
Retrograde degeneration, proximal to the axonal injury, results in peripheral displacement of the nucleus, dissolution of Nissl bodies, and enlargement of the cell body.
Deenervation of muscle fibers?
As a result of denervation, skeletal muscles undergo atrophy. Microscopically, denervation atrophy of skeletal muscle appears as small muscle fibers with decreased cross-sectional area, which are angulated or triangular and arranged in small groups (circled in image B).
BBB?
sometimes you want a drug to get by - such as if you have ALL - boys age 2 - 5 - Acute lymphoblastic leukemia
Medications requiring adequate CNS bioavailability therefore require intrathecal delivery to achieve a therapeutic level locally. Methotrexate (along with cytarabine and prednisone) can be administered intrathecally as CNS chemopreventive therapy in patients with ALL.
it is formed by 3 structures: astrocyte foot processes, basement membrane, and tight junctions between nonfenestrated capillary endothelial cells.
brain glial cells
Ependymal cells produce CSF. neuroectoderm
Microglia are the CNS’s macrophages. - mesoderm
Oligodendrocytes myelinate CNS neurons. - neuroectoderm
Schwann cells myelinate neurons of the peripheral nervous system. neural crest
Intrathecal injection?
Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF) and is useful in spinal anesthesia, chemotherapy, or pain management applications.
Astrocytes - protect BBB and?
Repair
Glial scar - gliosis (walling off of absess)
GFAP - if see this - know tumor is in astrocyte -
iquefactive necrosis created by microglia
provide structural support to the brain parenchyma. Days to weeks after cerebral infarction, astrocytes are activated and extend processes to surround the area of liquefactive necrosis, forming a glial scar. This phenomenon is known as gliosis and is analogous to the role of fibroblasts in walling off an abscess. Unlike fibroblasts, however, astrocytes do not secrete collagen, and it is the cytoplasmic processes themselves that provide structural support. Astrocytes are also involved in potassium metabolism and maintain the blood-brain barrier. They are the primary repair and support cells of the central nervous system (CNS), and they stain for glial fibrillary acidic protein (GFAP).
Microglia? Mesoderm
they migrate to areas of tissue damage to help clear away dead and dying cells. They also release cytokines that stimulate the immune system to respond to the area of injury. HIV-infected microglia fuse to form multinucleated giant cells.
Microglia are the macrophages of the central nervous system and produce the liquefactive necrosis cavities.
mesoderm of CNS?
microglia and the dura mater and the connective tissue of the peripheral nervous system (endo-, peri-, and epineuria).
endoderm?
The endoderm gives rise to the epithelial lining of the gastrointestinal tract, urogenital system, and respiratory tract. The majority of the gastrointestinal system, including the pancreas and liver, is endodermal in origin.
Neural crest ?
Neural crest cells give rise to several tissues of the nervous system, including peripheral ganglia, afferent sensory nerves (dorsal root), and Schwann cells.
The neuroectoderm
gives rise to the central nervous system neurons, most of the CNS glial cells (including oligodendrocytes, astrocytes, and ependymal cells), the posterior pituitary, and the pineal gland.
The surface ectoderm
is an embryologic structure that gives rise to the lens of the eye, epidermis, and the anterior pituitary.
HIV and the brain
microglia - multinucleated giant cells
HIV encephalopathy is caused by infection of macrophages and microglia in the brain.
neurons themselves are rarely infected in HIV.
HIV is not known to infect oligodendrocytes.
The histologic hallmark of HIV encephalopathy is the microglial nodule,
Microglia are macrophages of the central nervous system that, like other tissue macrophages, arise from monocytes in the bone marrow and migrate to their resident tissue site. It is postulated that HIV is carried into the brain by infected monocytes. Neurons themselves are not infected by HIV, although they may be damaged by inflammatory responses to viral products. The histologic hallmark of HIV encephalopathy is the microglial nodule, largely consisting of multinucleated giant cells (indicated by the arrow in the vignette image), which are formed by the fusion of HIV-infected microglial cells (shown in this image).
oligodendrocytes - JC virus
JC virus is a human polyomavirus that infects oligodendrocytes after it becomes reactivated. JC virus is often acquired in childhood and remains latent within most adults in the kidneys and lymphoid organs. However, if the immune system becomes severely compromised, such as in late stages of AIDS, JC virus can become reactivated, resulting in progressive multifocal leukoencephalopathy (PML), which leads to lysis of oligodendrocytes. Since oligodendrocytes are the myelin-producing cells within the central nervous system, their destruction by JC virus causes an appearance of small foci of demyelination within the subcortical white matter. Seizures, ataxia, aphasia, hemiparesis, or sensory deficits are common manifestations.
Nodes of Ranvier
voltage gated potassium channels?
Nodes of Ranvier are gaps in the myelin sheath that occur along myelinated axons. In between the nodes, ionic current is conducted via the axonal cytoplasm, as resistance to current flow is lower across the cell membrane than it is across myelin.
Here the current activates voltage-gated sodium channels in the membrane, allowing ions to flow into the cytoplasm and boost the propagating depolarizing signal. The repolarization phase is facilitated by the activation of voltage-gated potassium channels, resulting in outflow of potassium. Increased capacitance and decreased resistance at the nodes of Ranvier alter the action potential and result in this “jumping” of the action potential from one node to another, known as saltatory conduction.
The nodes of Ranvier are sites of high membrane capacitance relative to the myelinated axon segments. The higher membrane capacitance facilitates rapid action potential propagation.
Guillain-Barré syndrome
Campylobacter jejuni
is a common cause of gastroenteritis, the most common pathogen associated with Guillain-Barré syndrome. Cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, and recent immunizations are also risk factors.
Guillain-Barré syndrome is an autoimmune disease mediated by T lymphocytes that target Schwann cells
ascending paralysis and decreased deep tendon reflexes
Most cases occur 2–4 weeks after a respiratory or gastrointestinal infection.
thought to occur because of immune responses against nonself-antigens that are misdirected toward the host (molecular mimicry).
Guillain-Barré syndrome
Campylobacter jejuni
is a common cause of gastroenteritis, the most common pathogen associated with Guillain-Barré syndrome. Cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, and recent immunizations are also risk factors.
sudden-onset paralysis, which has progressed from her legs to her arms and face. This, combined with her diminished reflexes
Guillain-Barré syndrome is an autoimmune disease mediated by T lymphocytes that target Schwann cells
ascending paralysis and decreased deep tendon reflexes
Most cases occur 2–4 weeks after a respiratory or gastrointestinal infection.
thought to occur because of immune responses against nonself-antigens that are misdirected toward the host (molecular mimicry).
decreased vibratory sense in the feet. - callouses, lack of sense of vibration
Diabetes
Pacinian corpuscles are damaged. These receptors are mainly involved in perception of pressure, coarse touch, high-frequency vibration, and tension. They are often damaged in patients with diabetic neuropathy. Pacinian corpuscles are large, ovoid receptors, 1–2 mm long × 0.1–0.7 mm in diameter, and are found primarily in deeper layers of the skin, at joint capsules, serous membranes, and mesenteries.
Several mechanisms are involved in the pathophysiology of this condition. However, microvascular disease appears to be the most prominent contributor.
normal aging can cause
78 yo -gait instability, decreased speed of postural reflexes, and slowed reaction times. Vibration sensation is diminished. Six months later, he dies in an automobile accident. An autopsy reveals a loss of neurons, especially in the frontal and temporal lobes, the presence of neurofibrillary tangles, enlarged and calcified arachnoid granulations, and enlarged ventricles. Which of the following is most consistent with the history and autopsy findings?
The brain undergoes changes in gross appearance as well as cellular and molecular composition during the aging process. There is a progressive loss of neurons from the seventh decade on, with significant loss of small neurons of layers II and IV in the frontal and superior temporal regions. Neurofibrillary tangles, senile plaques, and calcified arachnoid granulations can all be seen in normal aged brain. Neurologic findings can include a decrease in the rate and strength of motor activity as well as a slowed reaction time. Vibration sensation diminishes. There appears to be a decline in cognitive function and memory, although not all elderly individuals exhibit such changes. However, many aspects of mental decline once viewed as part of normal aging are now believed to reflect underlying pathologies.
blocking potassium channels causes?
Drug A induces seizure activity in neurons. At rest, the membrane potential of these neurons is-68 mV. Application of drug A causes these neurons to depolarize to-55 mV. Which of the following is the most likely mechanism of action of this drug?
Select one:
a. Open CI- channels
b. Block Ca2+ channels
c. Block K+ channels Correct
d. Block Na+ channels
depolarization
any increase in K+ conductance serves to move the membrane potential from-68 mV to a value closer to-90 mV, and any decrease in K conductance will move membrane potential in the other direction, that is, to a value more positive than-68 mV.
increase of extracellular K+ - hyperpolarize or depolarize?
Increasing extracellular [K+] decreases the concentration gradient driving K+ out of neurons
The result is that the opposing electrical gradient for K+ at equilibrium also decreases, that is, equilibrium potential for K+ becomes less negative. The major determinate of membrane potential at rest is K+ ion flux. As equilibrium potential for K+ becomes more depolarized, resting membrane potential also becomes more depolarized.
Vincristine - chemotherapy med
Disruption of the neuronal cytoskeleton
nerve was crushed in the distal one third of the finger. Which of the following is most likely?
Within a day, Schwann cells will begin to break down myelin of the axon distal to the lesion.
Nucleus
= group of neuronal cell bodies united by similar functions
Tract = many axons grouped together, pass from a given nucleus
periferal nervous system includes what structures in the brain?
PNS includes Cranial and spinal nerves outside the CNS - one exception – optic nerve – it is very different from others, as is olfactory -
spinal cord
Spinal cord: 5 regions: Cervical cord (8 pairs of spinal nerves) Thoracic cord (12 pairs of spinal nerves) Lumbar cord (5 pairs of spinal nerves) Sacral cord (5 pairs of spinal segments)
2 enlargements of the spinal cord:
Cervical enlargement – brachial plexus
Lumbar enlargement - lumbar and sacral plexus
CNS -
Brainstem + Cerebellum + Cerebral Hemispheres
= Brain
Brainstem:
3 divisions:
Medulla (continuous with the spinal cord)
Pons (rostral to the medulla)
Midbrain (continuous with the diencephalon)
Cerebellum:
Dorsal to the pons
Attached to the the brainstem by peduncles
peduncles?
Cerebellum:
Dorsal to the pons
Attached to the the brainstem by peduncles
a large bundle of neurons that resembles a large stalk (the Latin pedunculus means “footstalk”) and stretches from the cerebrum to the pons. There are two cerebral peduncles, one on each side of the brainstem.
3 motor cortex areas?
primary (area 4) - least electrical current required
premotor (dancing)
suuuplementary (initiates)
prefrontal cortex
psychiatrists work here
judments - intellectual, emotional events
location of frontal eye field? voluntary horizontal eye movement HY
middle frontal gyrus gyrus extending into the inferior frontal gyrus and immediately rostral (IN FRONT OF) to the premotor region
ORBITAL gyrus - if you lose it - you lose your orbit - you become mean, disinhibited
disinhibits you - angry, aggressive
orbital gyrus INHIBITS - with out it one is uninhibited - a Mean Mo Fo
Broca’s speech area - Only in dominant (usually left) hemisphere
comprehension intact - hard to name objects, repeat words
Communication (speech) difficult - even gesturing or sign language
within inferior frontal gyrus
Difficulty in naming objects
Difficulty in repeating words
Comprehension is intact
– most aspects of speech – controls larynx, pharynx working together – “speech” means communication – if someone is using sign language and had never been able to speak – if he has a stroke – and trauma to Broca’s area – this person would also be affected –
deaf person who signs has damage in broca’s error - is there ability to communicate affected?
Yes. comprehension intact
Broca’s speech -
skip words “I doctor”
Aphasia
Aphasia – absence of speech – can’t name objects – Alzheimer’s can tell you how to use the object, but can’t name it.
insula - PAIN processing (not where first received), TASTE, Disgust
It tastes painfully Disgusting
Seen only when temporal lobe is pulled away
Lies within the depths of the lateral (Sylvian) sulcus
Convergence of temporal, parietal and frontal cortices
under temportal - disgusting area - smells, tastes, moral disgust
Reception and integration of taste sensation
Reception of viscerosensations
Processing of pain sensations
Vestibular functions
parietal lobe - mainly sensory
from central sulcus extends caudally to parietal occipital sulcus – imaginary line – only visible on medial surface of hemisphere
Post central gyrus - receives PAIN and TEMP sensations -
Somatotrpic organization – any person will experience sensations in a particular area -
lots of info received here – than transported to frontal cortex for analysis
Postcentral gyrus: PAIN, TEMPERATURE – receives info
Boundaries:
Anteriorly: Central Sulcus
Posteriorly: Postcentral Sulcus
Functions:
Primary receiving area for somesthetic (i.e., kinesthetic and tactile) information
Input is contralateral
Somatotopic organization (parallel to the motor cortex)
somatotopically organized /. As the stimulating electrode is moved across the precentral gyrus from dorsomedial to ventrolateral, movements are elicited progressively from the torso, arm, hand, and face (most laterally).
Parietal lobe - 3 parts
post central gyrus
Superior Parietal
Inferior Parietal 2 parts
Supramarginal gyrus:
Boundaries: superior to the posterior extent of the lateral sulcus
Angular Gyrus:
Boundaries: posterior to the supramarginal gyrus
Functions:
Input from auditory and visual cortices
Complex perceptual discriminations
superior - color and motor integration
processes info - sends to frontal
Job is to collect sensory info and pass to prefrontal cortex-
Integrates sensory and motor functions Aids in programming complex motor functions (with premotor cortex) Lesion: Apraxia (movement disorder) Sensory neglect (eg, left hemineglect)
Lesions in superior parietal?
Apraxia
Sensory neglect = contralateral
Lesion:
Apraxia (movement disorder)
Sensory neglect (eg, left hemineglect)
Sensory neglect
will show contralaterally – eg – see patient with a stroke – “someone stole my wedding ring” – show her her hand – and she says OK – I have my ring – but in a few minutes again – forgets about it – thinks it isn’t there – not that they are blind – they just don’t pay attention -
or perceptual neglect (including: auditory neglect, visual neglect and spatial neglect) is an impaired ability to perceive objects, so individuals do not attend to visual, auditory, or sensory stimuli coming from one side of the body. This may be caused by brain damage due to various causes.
apraxia - can move but not do complex movements - can’t hammer a nail
often see w/ Alzheimer’s
Inferior parietal lobe
– complex perceptual discriminations – eg – newborn baby – 7 days old – this area will react differently to music and human speech – already – only learned about these parts of the brain in the last 30 years
2 parts
Supramarginal gyrus:
Boundaries: superior to the posterior extent of the lateral sulcus
Angular Gyrus:
Boundaries: posterior to the supramarginal gyrus
Functions:
Input from auditory and visual cortices
Complex perceptual discriminations
Wernicke’s only in left hemisphere
if lesion - person won’t understand what is being said, what being asked –
Speech still fluent - but can’t understand
for understanding communication – only in left hemisphere – comprehension of spoken language and communication – if lesion - person won’t understand what is being said, what being asked –
where is wernicke’s located?
superior temporal gyrus + ventral parts of supramarginal and angular gyri
so if Broca’s intact and Wernicke not
Lesion (aka Wernicke’s [sensory]) aphasia):
Impairment of speech comprehension and repetition
Speech remains fluent -> Broca’s center is intact
can’t understand what being asked
in real life, see these two together a lot - but for exams need to know diff
Temporal lobe 3 guri - but a fourth area inside - mainly responsible for HEARING - 3 gyru
Heschl gyrus (on internal aspect)
Superior temporal gyrus
Middle temporal gyrus
Inferior temporal gyrus
temporral lobe functions
hearing (superior and Herschl) located on INSIDE
see moving objects (middle)
recognize faces - inferior
Functions:
Perception of auditory signals (primary auditory cortex, superior temporal gyrus + gyri of Heschl)
Perception of moving objects in the visual field (middle temporal gyrus)
Recognition of faces (inferior temporal gyrus)
Occipital - eyes in the back of your head - visual
Interpretation of the visual information
larger portion visible from medial surface
From eye – whatever you see – travels all the way back here and then goes back to prefrontal cortex
medial surface of brain
frontal, parietal, occipital
Paracentral - controls LOWER EXTREMITIES
paracentral -
continuation of the precentral and postcentral gyri on the medial side:
controls motor and sensory innervations of the contralateral lower extremity
– normal pressure hydrocephalus – IMPORTANT this area of brain, and disease
occipital lobe from medial aspect
Function: Visual receiving area (primary)
Anteriorly: Parietal-occipital sulcus (border with parietal lobe) Calcarine sulcus (fissure) - perpendicular to parietal-occipital sulcus, in the middle of the occipital lobe
Calculine sulcus
– very important area
– where initially all visual info comes
Cingulate Gyrus: limbic system (a part of)
above CORPUS COLOSUM
quick decisions, Empathy, compassion
where some of your emotions are controlled
quick fast decisions?
overreaction?
probably made by limbic not frontal cortex
Quick decisions made mostly by limbic decisions (running away from a rabid dog) – sometimes if too much stress, etc – limbic makes decisions for you - over-reaction – probably made by limbic and not frontal cortex
corpus colosum? Massive fiber pathway
Communication between hemispheres
Massive fiber pathway – all the grey matter above the corpus - corpus callosum is the white matter – connecting everything
Septum Pellucidum:
Forms medial wall of lateral ventricles
2 thin-walled membranes with cavity between them (cavity of septum pellucidum)
Boundaries:
Ventral: corpus callosum
Fornix - seahorse?
key role in cognition and episodic memory recall.
Transmission from hippocampal formation to the septal nuclei and hypothalamus
The fornix is a white matter bundle located in the mesial aspect of the cerebral hemispheres, which connects various nodes of a limbic circuitry and is believed to play a key role in cognition and episodic memory recall.
Hippocampus
- memory skills
need to sleep to develop memory
Amygdala
emotional map of your brain – fear of heights, spiders, all in the amygdala – aversion center –
The amygdala is recognized as a component of the limbic system, and is thought to play important roles in emotion and behavior. It is best known for its role in the processing of fear,
The amygdala is an almond-shaped structure in the brain; its name comes from the Greek word for “almond”. … Each amygdala is located close to the hippocampus, in the frontal portion of the temporal lobe. Your amygdalae are essential to your ability to feel certain emotions and to perceive them in other people.
Diencephalon:
Thalamus one of main centers – collects all sorts of info – major electric substation - the only system that can bypass this ? Olfactory!
Hypothalamus – controls all glands and smooth muscles – horner’s syndrome – Pancoast tumor –
KING Of autonomic system – any lizard will function similar to humans -
Below fornix
Structures in diencephalon:
Thalamus:
Sensory, motor, autonomic and emotional information passes through thalamus (↕ )︎
Hypothalamus:
Anterior and below thalamus
Visceral functions (t0, endocrine, feeding, drinking, emotional, sexual)
Hypophysis is attached to hypothalamus
inferior surface of brain structures
gyrus rectus (not clear function
Thought to be involved in higher cortical functions (esp. personality features)
lateral to this is the olfactory bulb and tract
Olfactory bulb:
Boundaries: lateral to gyrus rectus
Function: receive information from olfactory nerve (CNI)
Olfactory tract:
Boundaries: continuation of the tract from olfactory bulb
Branches:
Lateral (-> temporal lobe and limbic system)
Medial (-> limbic structures medially and contralaterally via anterior commissure)
Occipitotemporal gyrus
(aka fusiform gyrus):
Boundaries:
Medially: collateral sulcus
Laterally: inferior temporal sulcus
Function:
Not fully understood
Thought to be involved into recognition processes
Parahippocampal gyrus:
UNCUS - HOOK - brain edema - can kill you
In general – recognizes letters -
Memory encoding and retrieval
Boundaries:
Laterally: collateral sulcus
Inferiorly: lingual gyrus
Rostral part has a bulging – uncus
UNCUS – HOOK very important – brain edema – can affect uncul herniation and kill you -
Function:
Memory encoding and retrieval
Many of these regions are highly variabile from one person to another – so hard to test on re tests – gyru take on different forms, shapes
In general – recognizes letters -
Uncal herniation -
most common place of supratentorial herniation
Hippocampal formation and amygdala are situated deep to the cortex of the parahippocampal gyrus and uncus.
seizures in temporal lobe epilepsy.
Structures in this area (on this slide) have a very low threshold for induction of seizure activity and commonly the focus of the seizures in temporal lobe epilepsy.
Lingual gyrus: LOGIC
Vision processing (esp. letters) Analysis of logical conditions (eg, logical order of events)
Boundaries:
Rostrally: parahippocampal gyrus
Laterally: collateral sulcus
Medially: isthmus of cingulate gyrus + apex of cuneus
Function:
Vision processing (esp. letters)
Analysis of logical conditions (eg, logical order of events)
CT scans - hyperdense -
very white +1000 hyperdense bone…. blood (denser - lighter)
zero - water
very black -1000 hypodense air
isodense - tissue damage, appears basically the same as the surrounding brain,
Bone in CT: greatly attenuates x-rays
high CT number (appears white)
acute subarachnoid hemorrhage in CT is hyperdense (appearance similar to bone = whiter than surrounding brain)
Air in CT poorly attenuates x-rays
has a low CT number (appears black)
Area of ischemia (low O2 supply)
Hypodense (appearance shifted toward that of air) darker than the surrounding brain
When the lesion, or tissue damage, appears basically the same as the surrounding brain, it is specified as isodense
Would blood every look hyperdense on CT? YES! blood is dense - Hyperdense
vs air is not dense “hypodense”
infaract - lacking blood - thus darker
What does infarct in the brain mean?
Infarction refers to death of tissue. A cerebral infarction, or stroke, is a brain lesion in which a cluster of brain cells die when they don’t get enough blood.
Enhanced CTs - vasculature, iodine contrast
Iodinated contrast material injected intravenously
Iodine has a large atomic number and attenuates x-rays
Followed by CT examination
Vasculature is visualized as hyperdense (white) structures
Enhances neoplasms or areas of inflammation
contrast agent leaks from the vessels into the cellular spaces
Possible only if blood-brain barrier is broken down
Tumors, inflammation show varying degrees of enhancement or hyperdensity (varying degrees of whiteness)
3 major roles for CT - 3 H
hemorrage
hydrocephalus
herniation
MRIs
When undergoing an MRI examination
the patient becomes a magnet
all the protons align along the external magnetic field and spin at an angle with a certain frequency
MRIs in many flavors - many - know T1 and T2 - time function
T1 - spin lattice, white (matter INSIDE) bright, CSF dark, most lesions dark
T2 - spin spin = grey matter bright - CSF BRIGHT, most lesions bright
notes re MRI
Note!
Acute subarachnoid hemorrhage is poorly imaged by MRI on T1-weighted images
Some MRI sequences are sensitive for detection of acute bleeding, but other factors may limit this method of examination
Special MRI techniques can also determine if a brain infarct or ischemia is acute (about 1 to 3 hours old) or subacute (about 4 hours old or more)
Coronal scans =
viewed as though the clinician is facing the patient.
CT windows
Brain window – best for visualizing the brain structures
Subdural window – density of acute blood is visualized better than the brain structures
Stroke window – poor view on peripheral structures, better white/gray matter contrast
Bone window – visualizing bones
CT vs MRI
CT - more bone details, less tissue
BBB - do contrasts in blood get into brain?
not normally, but IF BBB broken will see that in CT with contrast
iodine as contrast?
Iodine is more dense than most tissue – greater attenuation
Early injection – assess vessels
Later injection – assess disruption of BBB
Complete injection – assess perfusion
reasons to not do CT
MRI can be tough on people with Kidney problems - gadolinium reaction -
Allergic reactions:
Hives, bronchospasm, laryngospasm
Severe reactions are rare (0.004%)
Nephrotoxicity:
Acute renal failure rare
Contraindicated in diabetics, myeloma, renal failure
Incidence reduced with hydration, low-osmolality contrast
Other:
Lactic acidosis in diabetics on metformin
Pregnancy
child - not want to give radiation
perikaryon
cell body
if dendrites don’t have voltage gated channels - and can’t generate action potential - how do they send the message along?
Receives signals from other neurons
Passively integrates dendritic and somatic signals; not excitable
WHAT DOES THIS MEAN? how pass it along?
neuron soma
Contains all major types of cellular organelles
Golgi complex
Nissl substance: abundant RER and free ribosomes support remodeling (synaptic plasticity) and constant secretory function (NT release)
Dispersed nuclear chromatin, reflecting high transcriptional activity
Axon hillock
Excitable membrane (has voltage-gated Na+ channels) Particularly low threshold for action potential generation High concentration of voltage-gated Na+ channels makes hillock exquisitely sensitive to changes in membrane potential
Axon doesn’t have…
No ribosomes (vs. dendrites)
Nodes of Ranvier
are unmyelinated gaps and the only excitable region of the axon
Action potentials jump from node to node through saltatory conduction
C fibers (smallest axons)
C fibers (smallest axons) are unmyelinated
Frequently protected by “sleeves” formed by glial cells
Excitable throughout their length
Cytoskeletal elements support extended, unique morphology and demanding transport requirements
axon terminal contains what kind of voltage gated channels?
Contains voltage-gated Ca2+ channels
NO voltage-gated Na+ channels
Passive spread of depolarization from axonal action potentials opens voltage-gated Ca2+ channels
Ca2+ entry into axon terminal initiates cascade that results in neurotransmitter release
boutons en passant.
boutons are found along the length of the axon
Other axons contain swellings, orvaricosities,that are not button-like but still can represent points of cell-to-cell information transfer.
Variations on basic structure of neurons
Sensory neurons may rely on specialized elaborations or cells to transduce specific types of non-neural inputs (eg, temperature, light, vibration)
Small neurons may function without an excitable membrane
Bipolar neurons of retina rely on passive spread of electrical signals from dendrites to terminal regions
Pseudounipolar neurons: support general somatosensory input HAVE NO DENDRITES
cell bodies in dorsal root ganglia of spinal cord and trigeminal ganglion
Pseudounipolar neurons are sensory neurons that have no dendrites, the branched axon serving both functions. The peripheral branch extends from the cell body to organs in the periphery including skin, joints and muscles, and the central branch extends from the cell body to the spinal cord.
One main process extends from soma and bifurcates into peripheral and central branch; main process is formed from fusion of two processes
Primary sensory neurons in somatosensory chain, with cell bodies in dorsal root ganglia of spinal cord and trigeminal ganglion
Bipolar neurons
special senses
Do not use action potentials in retina and olfactory system because bipolar neurons are small
Use action potentials in auditory and vestibular systems, with cell bodies in inner ear and axons projecting to brainstem
Two main processes extend from soma: one detects incoming signals; the other transmits information to the next neuron
various types of multipolar neurons
Interneurons: multipolar neurons with short axons that project locally
Projection neurons: multipolar neurons supporting elongated axons that can project great distances
Upper motor neurons: project from cerebral cortex and brainstem to lower motor neurons
Lower motor neurons: project to skeletal muscles
Association neurons: project from one gyrus or lobe to another within the same hemisphere
Synapse
a neuron may function simultaneously as presynaptic and postsynaptic element
chemical synapses
Chemical synapses are unidirectional
Each synaptic vesicle contains a fixed amount of neurotransmitter (called aquantum) – release depends on Ca2+ influx
boutons contain -
The bouton contains mitochondria, which supply energy for synaptic function, and also a prominent collection ofvesicles,which contain the neurotransmitter that will be released into the synaptic cleft. Vesicles are often aggregated near sites on the presynaptic membrane calledactive sites(orzones), which are the sites of neurotransmitter release.
adrenal medulla stimulated by
sympathetic preganglionic neurons.
neurotransmitters 60 types identified so far
Response is defined by the type of receptor
excitatory (glutamate)
inhibitory - GABA
syncytium - electric synapses
gap junctions, CONNEXONS
Allow for large numbers of cells to act as a syncytium (eg, cardiac muscle fibers)
Allow rapid communication with no synaptic delay
Presynaptic and postsynaptic neurons are physically connected by gap junctions formed by connexons
chemical vs electric synapses
Chemical synapses rely on diffusion of neurochemical from presynaptic to postsynaptic membrane
Electrical synapses are points of physical communication between presynaptic and postsynaptic membranes that allow direct ionic current flow
neuronal cytoskeleton
Microtubules
Neurofilaments
Actin filaments
Collagen fibrils provide support extracellularly but are not part of neural cytoskeleton
microtubules
Composed of protofilaments consisting of alternating α- and β-tubulin subunits that confer polarity on tubule
Stabilized by microtubule-associated proteins (MAP), including tau and MAP-2
TAU faulty processing in Alzheimer’s
Exist in longitudinal arrays in most dendrites and axons
In dendrites, both orientations are found
In axons, “+” ends are away from soma
Provide tracks
Kinesin out toward + end, Dynein back IN - retrograde
cancer fighting - in microtubules
Targeted by chemotherapeutic agents (eg, paclitaxel, vinblastine, and vincristine)
Stabilized by microtubule-associated proteins (MAP), including tau and MAP-2
Abnormalities in tau protein processing: hallmark of Alzheimer disease
neurofilaments - and diseases
ALS, Parkinsons’
Stabilize neuron shape
Major determinant of AXONAL diameter
Abnormal - neurodegenerative diseases ALS and amyotrophic lateral sclerosis and Parkinson disease.
Neurofilament and alpha-synuclein are major components in Lewy bodies.
Lewy bodies
are abnormal aggregations of protein that develop inside nerve cells, contributing to Parkinson’s disease (PD), the Lewy body dementias (Parkinson’s disease dementia and dementia with Lewy bodies), and some other disorders.
actin microfilaments
Comprise two strands of globular actin monomer
Homologous to thin filaments of striated muscle
Found near microtubules and plasma membrane and are associated with presynaptic terminals, dendritic spines, and growth cones
Interact with extracellular matrix and with other cells
Axonal transport
Fast anterograde transport - kinesin
Component A moves membrane proteins and neurotransmitters 200 to 400 mm/day
Component B moves larger elements (eg, mitochondria) 50 to 100 mm/day
Slow anterog
Slow anterograde transport
Regrowth of damaged axons: depends on slow transport to supply cytoskeletal materials
Moves soluble proteins :
Cytoskeletal proteins, neurofilament proteins, soluble NT synthesizing enzymes, and proteins not membrane-bound or within organelles)
0.2 to 8 mm/day toward terminal regions
Limits damaged axon regrowth to 1 to 4 mm/day
Retrograde axonal transport
Moves vesicles, membrane-bound organelles, and peripherally endocytosed growth factors back to soma
Rate: 200 to 300 mm/day along microtubules using dynein motors
Allows peripheral cellular components to be degraded and recycled
Rabies, tetanus
Unlike the rabies virus, which is replicated in the cell body, the tetanus toxin is diluted as it passes from cell to cell. In spite of this dilution effect, patients infected withC. tetanimay have a range of neurologic deficits.
Rabies virus
Replicates in muscle tissue (site of a bite by a rabid animal)
Taken up by axon terminals
Retrogradely transported to cell body
From CNS transported to the salivary glands - > saliva
Tetanus toxin is taken up by axon terminals
Retrogradely transported to cell body
Released by cell body
Taken up by other neurons
research re axonal transport?
Horseradish peroxidase - retrograde
Radioactively labeled aminoacids and wheat germ agglutinin (WGA-HRP) - anterograde
Horseradish peroxidase(HRP) or afluorescent substance are used in research of the retrograde transport
Radioactively labeled aminoacids and wheat germ agglutinin (WGA-HRP) are used in research of the anterograde transport
Electrical Properties of Neurons
Negatively charged (proteins inside) Membrane is selectively permeable to certain ions (ion channels) Channels react to variety of stimuli
glial cells - majority in CNS are glial
macroglia - astro, olig - neuroectoderm
schwann - neural crest
microglia - mesoderm
ependymal - neuroectoderm ??
astrocyte end-feet.
Astrocyte end-feet join together to completely line the interfaces between the CNS and other tissues.
The outer surface of the brain and spinal cord, where it meets the inner surface of thepia mater(the innermost of the meningeal membranes that enclose the CNS), is covered with a coating of several layers of joined end-feet called theglia limitans(or glial limiting membrane). Similarly, every blood vessel in the CNS is jacketed by a layer of end-feet that separates it from the neural tissue.
astrocytes GFAP
MC brain tumor
found in white matter, grey matter -
Astrocytes occur throughout the CNS. They are highly branched cells with processes that contact most of the surfaces of neuronal dendrites and cell bodies as well as some axonal surfaces and synapses.
function of astroycytes - What DON”T they do?? LOL
they don’t do what the other glial cells do
Maintain stable brain environment, transport nutrients
Buffer ions in extracellular space (pH), K+ metabolism
Help remove NTs released by active neurons (esp. glutamate)
Produce: IL-1, TNF-α, thrombospondins, cholesterol, LP, d-serine
End-feet surround brain capillaries, take up glucose, and promote formation of blood-brain barrier
During neuronal damage, can proliferate and phagocytose dying neurons, form glial scar
Radial glia: guide migration of neurons, direct outgrowth of axons in the developing brain
Fibrous astrocytes: found in white matter
Protoplasmic astrocytes: found in gray matter
Glial fibrillary acidic protein(GFAP) – marker of astrocytes
MC brain tumor?
Glioblastoma multiforme: high-grade (ie, very malignant) astrocytoma; the most common primary brain tumor.
glial scar
Note! When injury to the CNS results in destruction of cells, the space created by the breakdown of debris is filled by proliferation or hypertrophy (or both) of astrocytes, resulting in the formation of anastrocytic (glial) scar.That astrocytes retain the ability to proliferate in the mature brain (and thus are more susceptible to events that disrupt the control of cell division) explains why the majority of CNS tumors are of astrocytic origin.
astrocytes can secrete
In disease processes, astrocytes may secrete cytokines and immune mediators such as interleukin (IL)-1, tumor necrosis factor-α, and prostaglandin. Thus astrocytes as well as microglia contribute to the regulation of inflammatory processes in the CNS. In development, astrocytes induce synapse formation through their secretion of thrombospondins. Thrombospondins are a family of extracellular matrix proteins that bind to neuronal surface molecules (calcium channel subunits, integrins, and neuroligin synaptic adhesion proteins). Other astrocyte products, such as cholesterol and lipoproteins, are also thought to enhance synaptic plasticity.
astrocytes secrete glutamate NT - excitatory
also GABA - inhibitory
D-serine NMDA
ATP - used w/ adenosine for sleep wake cycle
ammonia enzyme produces glutamine - enzyme glutamin synthetase
Amino acid neurotransmitter glutamate is taken up by astrocytes and is then inactivated by the enzymatic addition of ammonia to produce glutamine (catalyzed by the enzymeglutamine synthetase). Glutamine released from astrocytes can be taken up and reconverted to glutamate in neurons. This astrocytic pathway also detoxifies ammonia in the CNS.
D-serine binds to neuronalN-methyl-d-aspartate (NMDA) receptors and modulates synaptic activity.
Astrocytes also release other neurotransmitters. The inhibitory neurotransmitter GABA is released from astrocyte anion channels. Its sustained mode of release causes tonic inhibition of synapses in the surrounding area. In contrast, adenosine triphosphate (ATP) is released by astrocytes in response to neuronal signaling. It is metabolized to the neurotransmitter adenosine, which is involved in cellular energy regulation and the sleep-wake cycle.
BBB end feet -
physical complex of endothelium, basal lamina, and astrocyte end-feet
Water, gases, and lipid-soluble small molecules can diffuse
but other substances must be carried across by transport systems, and their exchange is highly selective. This selectivity is further enhanced by a reduction in pinocytotic transport.
The blood-brain barrier is of major clinical importance because it largely excludes many drugs from the CNS.
In the CNS, vessels are induced by the surrounding jacket of astrocyte end-feet to form extensive tight junctions, so solutes can reach the neural tissue only by passing through the endothelial cells (Figure A).
The resulting restricted exchange constitutes the blood-brain barrier. In a strict sense, the blood-brain barrier is formed by the tight junctions of the endothelium. However, many people refer to the blood-brain barrier more inclusively as the physical complex of endothelium, basal lamina, and astrocyte end-feet surrounding each CNS vessel. Water, gases, and lipid-soluble small molecules can diffuse across the endothelial cells, but other substances must be carried across by transport systems, and their exchange is highly selective. This selectivity is further enhanced by a reduction in pinocytotic transport. In most tissues of the body, a high level of pinocytotic activity by endothelial cells transports solutes nonspecifically from the blood plasma to the perivascular space. In contrast, endothelial cells of capillaries in most parts of the CNS show little pinocytotic activity. The blood-brain barrier is of major clinical importance because it largely excludes many drugs from the CNS.
oligodendrocyte myelinates
“Fried egg”
Oligodendroglioma: rare tumor of cortical white matter, frequently leading to seizures
Destroyed in slow viral diseases, including progressive multifocal leukoencephalopathy
Affected in multiple sclerosis
acoustic neuromma?
Schwann cell tumor of CN VIII
Schwann cell myelinates one segment of a single axon
Secrete growth factors critical to regeneration of damaged PNS axons
Loss of myelin characterizes several neuropathies, including acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome)
Guillain-Barré syndrome is thought to be caused by a problem with the immune system, the body’s natural defence against illness and infection.
microglia Residents - fight infection, meningitis
susceptible to HIV-1 infection
Toxic environment generated by dying microglia may be direct cause of CNS involvement and dementia associated with human immunodeficiency virus type 1 (HV-1) Infection
HIV-infected microglia fuse to form multinucleated GIANT cells in CNS
Arise from monocytes derived from bone marrow (mesodermal origin)
Migrate into brain during development and become resident microglia
Transformed into activated microglia to phagocytose dying cells in response to damage within CNS (esp. infections, meningitis)
microglia are versatile
such as viral encephalitis caused by human immuno- deficiency virus-1 (HIV-1), subacute sclerosing panencephalitis, lead encephalopathy, and neurosyphilis, microglia withdraw and reshape their processes to form long rod cells closely apposed to affected neurons. In cases of trauma or severe tissue injury, they become motile, ameboid phagocytes capable of migrating to the site of injury and proliferating. At the injury site, they phagocytose tissue debris.
Microglial activation can be harmful.
For example, in bacterial meningitis in children, as microglia phagocytose particles of bacteria killed by penicillin, they are stimulated to secrete IL-1β.
IL-1β acts on endothelial cells to loosen their tight junctions, allowing leukocytes and blood plasma to enter CNS tissue, escalating the inflammation to a level that can be fatal. When researchers and physicians pre- vented this secondary inflammation by administering steroids before giving penicillin, microglial cytokine secretion was inhibited, and the survival rate for bacterial meningitis in children vastly improved.
Ependymal Cells
Choroid epithelial cells: specialized ependymal cells that produce cerebrospinal fluid (CSF)
Most ependymocytes have cilia and/or microvilli at apical processes that beat to move CSF
Tanycytes move selected molecules from blood to CSF
Ependymal cells, similar to all other neuroglia, are derived from a layer of embryonic tissue known as neuroectoderm. Ependymal cells and their epithelial derivatives of the choroid plexus have several important functions.
Tanycytes 3rd and 4th ventricle
move selected molecules from blood to CSF
third ventricle of the brain, and on the floor of the fourth ventricle and have processes extending deep into the hypothalamus. It is possible that their function is to transfer chemical signals from the cerebrospinal fluid to the central nervous system.
Wallerian degeration
Wallerian degeneration occurs distal to a point of severe axonal damage.
C, Chromatolysis follows.
D, Reinnervation of target may occur within the peripheral nervous system
Axonal degeneration distal to point of severe axonal damage
Nerve terminal fills with clumps of neurofilaments and disrupted mitochondria
Contact with postsynaptic membrane is lost, and axon segment distal to injury withdraws
Glial cells invade and phagocytose debris
A Nissl body, also known as Nissl substance - site of protein synthesis
and Nissl material, is a large granular body found in neurons. These granules are of rough endoplasmic reticulum (RER) with rosettes of free ribosomes, and are the site of protein synthesis.
chromatolysis
Anterograde transneuronal degeneration: when a neuron dies, downstream synaptic target neurons may die
Retrograde transneuronal degeneration: when a neuron dies, upstream synaptic partners may die
within soma: cell body swells, nucleus moves to side of soma, rough endoplasmic reticulum disintegrates
Neuron may survive: if neuron successfully reinnervates or if axotomy does not damage all terminals, chromatolysis may reverse.
Neuron may die: neurons without functional terminal frequently undergo apoptosis
axonal regeneration
Actively inhibited within CNS:
Oligodendrocytes actively inhibit neurite outgrowth
Reactive astrocytes cause glial scarring, which interferes with nerve regrowth
Fewer chemotropic factors are available in CNS.
May occur in PNS:
Growth cones sprout from proximal axon stump
Schwann cells and extracellular elements of remaining distal stump produce chemotropic factors that promote axon regrowth
Axons may reinnervate muscles, although target specificity may not be perfect
Some functional motor control of denervated muscle returns.
Resting membrane potential (RMP)
Normally, does not change with minor perturbations, such as action potential generation
RMP is determined primarily by K+ gradient
Steady-statemembrane potential
Results primarily from constant net flux of K+ions out of the neuron and smaller net flux of Na+into the neuron
Depends on action ofNa+/K+ATPasepump that maintains both K+and Na+ concentration gradients
lethal injections
how work?
Infusion of K+-based, rather than Na+-based, solutions decreases K+ gradient, causing K+ equilibrium potential and RMP to become more positive
Take-home message: intravenous K+-based solutions cause cardiac fibrillation and death
Eg, lethal injection with KCl depolarizes excitable cardiac tissues, causing fibrillation and death
Graded potentials
Graded” = larger signal → more channels affected → larger amplitude change in membrane potential
Move across membrane by electronic (passive) conduction
Signal amplitude diminishes as depolarizing wave travels from the source
Graded potentialsSubtypes
End-plate potentials:
Occur at motor end plate when ACh is released from the nerve terminals binds with muscle receptors to open Na+/K+ channels
Receptor (generator potentials):
Occur at the sensory region of primary sensory neurons that are exposed to an adequate stimulus
Excitatory postsynaptic potentials (EPSPs): produced at dendrites and somas in response to excitatory neurotransmitters
Inhibitory postsynaptic potentials (IPSPs): are produced at dendrites and somas in response to inhibitory neurotransmitters
Prototypical peripheral nervous system (PNS) sensory neuron
A, Larger or longer incoming stimulus causes larger or longer graded potential
B, Larger graded potentials are coded as increased action potential frequency, whereas longer graded potentials cause a longer train of action potentials
C, Action potentials carry information from the source to the terminal region without signal degradation. In PNS sensory neurons, the source is the trigger zone; in central nervous system neurons, the axon hillock is the source
D, Neurotransmitter release increases as terminal depolarization increases
Graded potentialsSummation
temporal
spatial - (arrive simulateneously)
Temporal summation occurs when a second graded potential arrives in time to build on the first, creating a larger graded potential
Spatial summation occurs when two graded potentials arrive simultaneously on a region of a neuron and add together
, Neuron X excites a dendrite on neuron Y two times (arrows). Graded potentials can be measured some distance away. However, because the time constant of the membrane is short, the first excitatory postsynaptic potential (EPSP) has died before the second arrives, and they do not add.
B, Time constant of the membrane is longer, so the first EPSP has not died before the second arrives. The second EPSP builds on the first, causing a larger depolarization.
action potentials
All-or-none if a membrane depolarizes to threshold
Actively transmitted over long distances from cell body to nerve terminal without signal degradation
Refractory periods:
Prevent a second action potential during the first action potential
During absolute refractory period (immediately after action potential), neuron cannot produce another action potential
During relative refractory period (after absolute refractory period), only a strong stimulus will induce an action potential
Action potentials do not add:
Information is coded in the frequency and pattern of action potentials
Ion pumps maintain necessary ion gradients for generation of action potentials (eg, Na+/K+ ATPase)
Generated by excitable membrane, containing voltage-gated ion channels
Na+channel opening depolarizes membrane
Channels respond in a probabilistic fashion to membrane potential
At more depolarized membrane potentials, the probability that a given channel will be “open” is higher
K+channel opening accelerates repolarization of membrane
myelination
See info below ???
Electrical insulation surrounding axons
Increases membrane resistance of axons
Increased membrane resistance increases length constant, which allows current generated by action potentials to travel further
Length constant allows nodes of Ranvier to be spaced far apart on an axon.
Decreases membrane capacitance by increasing charge separation
Decreased membrane capacitance decreases membrane time constant, allowing membrane to charge and discharge more rapidly
Rapid membrane charging allows for faster conduction of action potentials
Most peripheral nervous system (PNS) axons of at least 1 μm diameter and most central nervous system (CNS) axons of at least 0.25 μm are myelinated.
nodes of ranvier
Demyelination (eg, from multiple sclerosis) leads to redistribution of voltage-gated channels throughout length of axon.
Segments of excitable membrane that interrupt myelination every 0.5 to 1.0 mm intervals
Allow for saltatory (“jumping”) conduction
Neurons conserve energy by producing action potentials only at nodes
Increases rate of action potential conduction
Voltage-gated Na+ channels stabilized at nodes
Voltage-gated K+ channels stabilized adjacent to nodes
Disorders of myelination in the PNS:
Acute inflammatory demyelinating neuropathy (Guillain-Barré syndrome)
Diabetic neuropathy
Peroneal muscular atrophy (Charcot-Marie-Tooth disease)
Guillain-Barré syndrome
COMPYLOBACTER JEJUNI
mimicry
immune system knows they are foreign
can happen in two weeks! often there was an infection a couple weeks before
don’t know what causes it
Most common immune-mediated disorder to affect peripheral myelin
Frequent presentation: weakness ascending rapidly from legs to arms and finally to face, without sensory involvement.
Progression:
May be less than 2 weeks from first signs of weakness to respiratory insufficiency requiring ventilatory support
stocking-and-glove distribution of sensory loss
Diabetes mellitus: damages peripheral myelin and axons
PNS
Some diabetic neuropathies cause peripheral demyelination
May affect sensory, motor, or autonomic systems or a combination
Signs: stocking-and-glove distribution of sensory loss
Aka Charcot-Marie-Tooth disease PNS
Family of genetic disorders affecting peripheral myelin
Progression: slow, causing muscle weakness and mild sensory loss
Signs: “stork-like legs, “ clumsiness, and eventual difficulty with fine motor skills
MyelinOligodendrocytes
Inflammatory progressive disorder destroying central myelin
Multiple lesions disseminated in space and time, commonly periventricular (near a ventricle), viewed on magnetic resonance imaging
Cause: unknown, but genetic susceptibility, autoimmunity, and viral infections have been implicated
Glia responsible CNS myelination
One oligodendrocyte provides myelin to up to at least 40 different axons
MC condition affecting central myelination = multiple sclerosis
Multiple sclerosis: destroys CNS myelin, causing sensory and motor deficitsThird or fourth decade of life
Incidence is slightly higher in women
Blurry or sudden loss of vision:
Aka optic neuritis, frequent initial finding
Ataxia (the loss of full control of bodily movements). and scanning speech: cerebellar involvement
Urinary incontinence, muscle weakness, and paresthesias:
demyelination of long tracks
Jerky eye movements: internuclear ophthalmoplegia from pontine demyelination in medial longitudinal fasciculus
Scanning speech and MS
is a type of ataxic dysarthria in which spoken words are broken up into separate syllables, often separated by a noticeable pause, and spoken with varying force.
Electrical Synapses
a connexin hemichannel, is an assembly of six proteins called connexins that form the pore for a gap junction between the cytoplasm of two adjacent cells. This channel allows for bidirectional flow of ions and signaling molecules.
Rapid but limited communication
Membranes of the presynaptic and postsynaptic neurons contain connexons formed by specialized proteins that link across the space, separating the cells
Connexons form a gap junction (aqueous pore of communicating cytoplasm)
No delay and minimal modification of signal, because flow of ions between cells is direct
Chemical synapses
Slower than electrical but allow for more complex signaling
Use chemical molecules (neurotransmitters) for communication
Release of NT from presynaptic terminal requires calcium:
Calcium enters through voltage-dependent calcium channels.
Presynaptic voltage-dependent Ca2+ channels open as action potentials depolarize the terminal
Synaptic cleft: space between presynaptic axon terminal and postsynaptic membrane through which transmitter diffuses
Postsynaptic responses depend on receptor
Types of chemical synapses
Several neurotransmitters can activate directly gated channels including glutamate, acetylcholine, y-aminobutyric acid (GABA), glycine, and serotonin
Benzodiazepines: potentiate chloride conductance through GABA receptors within CNS
Direct gated:
Binding of neurotransmitter opens or closes an ion channel within the receptor
rapid change in postsynaptic membrane potential (EPSP or IPSP)
Indirect gated:
Binding of neurotransmitter activates second-messenger pathways
Binding of neurotransmitter activates second-messenger pathways by way of guanosine triphosphate-binding (G proteins).
Signal transduction pathways activated by second messengers may have multiple and lasting effects ???
Second-messenger pathways: cyclic adenosine monophosphate, phosphoinositide, and prostaglandin
Nonsteroidal anti-inflammatory drugs (aspirin and indomethacin): inhibit prostaglandin formation
Botulinum toxin inhibits muscle contraction presynaptically by decreasing the amount of ACh released into the neuromuscular junction. In contrast, curare acts post-synaptically, blocking the nicotinic ACh receptors
and preventing the excitation of the muscle cell membrane. Tetrodotoxin blocks voltage-sensitive Na! channels, impacting both the initiation and the propagation of action potentials in the motor neuron. Both ACh and neostigmine stimulate muscle contraction.
Botulinum toxin inhibits the release of acetylcholine from a -motoneurons by blocking one of the proteins responsible for the fusion of the synaptic channel with the presynaptic membrane. Botulinum toxin also inhibits the release of acetylcholine from the neurons of the autonomic nervous system. Botulinum and tetanus toxin are released from the same class of bacteria (Clostridium ). Tetanus toxin produces an increase in skeletal muscle contraction by blocking the release of inhibitory neurotransmitter from spinal interneurons.
What is curare used for?
Curare, drug belonging to the alkaloid family of organic compounds, derivatives of which are used in modern medicine primarily as skeletal muscle relaxants, being administered concomitantly with general anesthesia for certain types of surgeries, particularly those of the chest and the abdomen.
Bradycardia - mushroom poisoning
slower than normal heart rate. The hearts of adults at rest usually beat between 60 and 100 times a minute. If you have bradycardia (brad-e-KAHR-dee-uh), your heart beats fewer than 60 times a minute. Bradycardia can be a serious problem if the heart doesn’t pump enough oxygen-rich blood to the body.Nov 13, 2019
Myasthenia gravis is an autoimmune disease
damage receptors
in which antibodies damage postsynaptic nicotinic acetylcholine
receptors. This damage prevents the firing of an action potential in the postsynaptic membrane.
Tensilon is a readily reversible acetylcholinesterase inhibitor that increases acetylcholine levels in the neuromuscular junction, thereby increasing the strength of muscle contraction.
botulism toxin - blocks SNARE like proteins
hence muscles don’t fire
Tetanus toxin blocks release of inhibitory NT
produces an increase in skeletal muscle contraction by blocking the release of inhibitory neurotransmitter from spinal interneurons.
Repetitive stimulation of a skeletal muscle fiber will cause an increase in contractile strength due to an increase in which of the following?
Repetitive firing increases the amount of SEC stretch by maintaining cross-bridge cycling for a longer period of time.
The duration of cross-bridge cycling
Each time a skeletal muscle fiber is stimulated by an a motoneuron, enough Ca2+ is released from its sarcoplasmic reticulum to fully activate all the troponin within the muscle. Therefore, every cross bridge can contribute to the generation of tension. However, the transmission of force from the cross bridges to the tendon does not occur until the series elastic component (SEC) of the muscle is stretched.
Repetitive firing increases the amount of SEC stretch by maintaining cross-bridge cycling for a longer period of time. Repetitive firing increases neither the concentration of Ca2+ within the myoplasm, the number of myofibrils that are activated, nor the magnitude of the end-plate potential. Because all of the cross bridges are activated each time a skeletal muscle fiber is activated, an increase in Ca2+ concentration would have no effect on muscle strength. Limitation in rising from a seated position or combing hair is suggestive of proximal muscle weakness, characteristic of dermatomyositis.
myasthenia gravis
?? The cautious use of this test in patients with heart failure results from the possibility that the decreased breakdown of acetylcholine released by the vagus nerve could decrease heart rate to dangerously low levels.
wouldn’t it increase?
The drug used to test for myasthenia gravis is an acetylcholine esterase inhibitor such as neostigmine. The drug prevents the breakdown of acetylcholine, increasing the duration of time acetylcholine remains in the synaptic cleft. Because acetylcholine can bind to the endplate receptors for a longer time, the magnitude of the end-plate potential increases, increasing the probability of it generating an action potential. The greater the action potential force rate, the greater the source of muscle contraction. Increasing the amount of acetylcholine released by the a motoneurons, by increasing the affinity of the skeletal muscle receptors for acetylcholine or increasing the discharge rate of a motoneurons could cause a similar effect. However, none of these changes would affect heart rate. The cautious use of this test in patients with heart failure results from the possibility that the decreased breakdown of acetylcholine released by the vagus nerve could decrease heart rate to dangerously low levels.
The amount of force produced by a skeletal muscle can be increased by which of the following?
Maximum summation is called tetanus
how to increase interval between contractions?
Decreasing the interval between contractions
When the interval between skeletal muscle contractions is small, the force produced by the two successive contractions will summate. The shorter the interval between the contractions, the greater the summation will be. Maximum summation is called tetanus.
Decreasing extracellular Ca2+ will increase the excitability of skeletal muscle fibers but does not have a direct effect on contractile force. Increasing the Mg2+ concentration will decrease skeletal muscle excitability. Increasing the preload beyond 2.2 mm decreases the overlap between thick and thin filaments and therefore decreases the force of contraction. Increasing the activity of acetylcholine esterase enhances the hydrolysis of ACh and therefore decreases the likelihood that muscle contraction will be initiated.
Which adrenergic receptor produces its stimulatory effects by the formation of inositol 1,4,5-triphosphate (IP3) and an increase in intracellular [Ca2+]?
Select one:
a.
a1 Receptors
Adrenergic α1 receptors produce physiologic actions by stimulating the formation of inositol 1,4,5-triphosphate (IP3) and causing a subsequent increase in intracellular [Ca2+]. Both β1 and β2 receptors act by stimulating adenylate cyclase and increasing the production of cyclic adenosine monophosphate (cAMP). α2 Receptors inhibit adenylate cyclase and decrease cAMP levels. Muscarinic and nicotinic receptors are cholinergic.
Pheochromocytoma
Antagonist drug
Phenoxybenzamine decreases blood pressure by acting as an α1 receptor antagonist, thus decreasing intracellular IP3/Ca2+.
is a tumor of the adrenal medulla that secretes excessive amounts of norepinephrine and epinephrine. Increased blood pressure is due to activation of α1 receptors on vascular smooth muscle and activa- tion of β1 receptors in the heart. Phenoxybenzamine decreases blood pressure by acting as an α1 receptor antagonist, thus decreasing intracellular IP3/Ca2+.
Myasthenia gravis (MG)
caused mainly by antibodies against muscle nicotinic acetylcholine receptors
What are the muscarinic effects? parasympathetic activation - so diahhrea bladder stim, pupils constrict
Clinical Effects on the Peripheral Nervous System Due to Excessive Stimulation of Muscarinic Receptors
Bladder stimulation, sphincter relaxation.
Bronchospasm.
Miosis (pupillary constriction), eye pain due to ciliary spasm.
Nausea, vomiting, cramps, diarrhea.
neostigmine
MG drug - enhance communication between nerves and muscles. …
Curare
first paralytic used in anesthesia,
Atropine
used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery
aspirin
irreversibly inhibits both forms (but is weakly more selective for COX-1). It does so by acetylating the hydroxyl of a serine residue. Normally COX produces prostaglandins, most of which are pro-inflammatory, and thromboxanes, which promote clotting.
How does aspirin work as an anticoagulant?
Anticoagulants such as heparin or warfarin (also called Coumadin) slow down your body’s process of making clots. Antiplatelet drugs, such as aspirin, prevent blood cells called platelets from clumping together to form a clot.
Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines)
are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system.
agonists - mimic NT
can be full or partial - binds in same place
Receptors - where do they bind to NT?
on their R arm
ACH is made how?
cholineacetyltransferase
CHOLenergic (AcetylCHOLINE)
choline + acetyl Coa
AchE (esterase) degrades - removes NT (Ach) from receptor
Where does DOPAMINE become a NT?
made in brain - substantia nigra, ventral tegmental, hypothalamus
kidney (renal vasculature - VASODILATES), CNS, ganglia, heart
also works in heart - Does dopamine increase blood pressure?
Dopamine (dopamine hydrochloride) is a catecholamine drug that acts by inotropic effect on the heart muscle (causes more intense contractions) that, in turn, can raise blood pressure. At high doses, Dopamine may help correct low blood pressure due to low systemic vascular resistance.
What triggers dopamine release?
It is released during pleasurable situations and stimulates one to seek out the pleasurable activity or occupation. This means food, sex, and several drugs of abuse are also stimulants of dopamine release in the brain, particularly in areas such as the nucleus accumbens and prefrontal cortex.
Where’s tyrosine (for dopamine) made?
dopaminergic and adrenergic neurons, adrenal medula
Norephinephre made in adrenergic neurons and adrenal medulla -
epinephrine made in adrenal medulla
DOPA problems
Parkinons’s - degeneartion of dopaminergic neurons that use the D2 receptors
SCHIZOPhrenia - involves INCREASED levels of D2 receptors
cocaine - NE re uptake
inhibitor
Degradation of NE, EPH, Dopamine
peripheral tissues COMT
presynaptic nerve terminal MAO (reuptake)
some excreted in urine - VMA, HVA, normetanephrine, metanephrine
PHEOCHROMOCYTOMA
, a tumor of the adrenal medulla that secretes catecholamines (mostly NE, not Epi), urinary excretion of VMA is increased.
Nitric oxide (NO)
Arginine → citrulline + NO (NO synthase)
Released by vascular endothelial cells (endothelium-derived relaxation factor [EDRF]); plays an important role in blood pressure regulation by promoting vascular smooth muscle relaxation
By promoting vascular smooth muscle relaxation and increasing blood flow, NO stimulates penile erection in patients with erectile dysfunction (ED).
permeant gas
short-acting inhibitory neurotransmitter
in the gastrointestinal tract and the central nervous system.
Arginine → citrulline + NO (NO synthase)
NO simply diffuses from the presynaptic terminal to its target cell
serotonin made from?
into melatonin -
tryptophan - > serotonin -> melatonin
tryptophan -> niacin -> NAD+
lack of tryptophan - can’t reabsorb neutral AA
Hartnup disease is a genetic disorder that reduces tryptophan absorption, leading to pellagra. Alterations in protein metabolism may also produce pellagra-like symptoms.
other NT
histamine (from histidine
glycine - inhibitory - found spinal cord and brain stem - increases Cl_ conductance (like GABA)
found in
synthesized from histidine (histidine decarboxylase) - in neurons of the hypothalamus, in nonneural tissue (mast cells of the gastrointestinal tract)
NT Glutamate - EXCITATORY
four types of receptors - 3 ionotropic - including NMDA found thruout CNS,
1 metabotropic receptor
NT GABA - inhibitory
from glutamic acid
KREB’s cycle
2 types of receptors ionotropic and metabotropic - both hyperpolarize with Cl-
degraded by GABA transaminase to enter the TCA KREB’sCycle
2 types of R:
GABAA- linked to a Cl− channel (ionotropic) – increases Cl− conductance - hyperpolarizes (inhibits) the postsynaptic cell
GABAB - coupled via a G protein to a K+ channel (metabotropic) - increases K+ conductance, hyperpolarizes the postsynaptic cell
GABAa site of what drugs being used to inhibit?
benzodiazepines and barbiturates in
the CNS
Huntington’s missing?
Synthesized from glutamic acid (glutamic acid decarboxylase)
riad of movement disorder:
chorea, (sudden uncoordinated movements)
behavioral abnormalities (aggressiveness, apathy or depression),
dementia.
Auto Dom, chrom 4
Anticipation
GABA
associated with GABA deficiency in the projections from the striatum to the globus pallidus. ANTICIPATION in this disease
lack of GABA-dependent inhibition of neural pathways.
The mutation is on chromosome 4 and is dominant in inheritance, with 100% penetrance
disorder caused by trinucleotide repeat expansions >40 CAG repeats
The mutated huntingtin protein forms insoluble plaques with cross-beta structure
Huntington disease manifests with the triad of movement disorder:
chorea, (sudden uncoordinated movements)
behavioral abnormalities (aggressiveness, apathy or depression),
dementia.
four snare proteins?
synaptobrevin, syntaxin and SNAP-25, synaptotagmin
NT binds it’s own receptor?
can trigger other events to occur inside the cell
The fo
NT binds it’s own receptor?
can trigger other events to occur inside the cell
major classes of NT receptors
Adrenergic: α1A, α1b, α1c, α1d, α2a, α2b, α2c, α2d, β1, β2, β3
Cholinergic:
Muscarinic: M1, M2, M3, M4, M5;
Nicotinic: muscle, neuronal (α-bungarotoxin-insensitive), neuronal (α-bungarotoxin-sensitive)
Dopaminergic: D1, D2, D3, D4, D5
GABAergic: GABAA, GABAB1a, GABAB1δ, GABAB2, GABAC
Glutaminergic: NMDA, AMPA, kainate, mGluR1, mGluR2, mGluR3, mGluR4, mGluR5, mGluR6, mGluR7
Histaminergic: H1, H2, H3
Opioid: μ, δ1, δ2, κ
Serotonergic: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7
Glycinergic: Glycine
can parasympathetic use any nt receptors other than cholinergic?
NO - thus always using ACH - as NT
NT are ALWAYS Muscarinic
G protein NR receptor process
ligand, 7 crosses,
G protein -
heterotrimeric - have three different subunits: α (When bind GDP is inactive, when binds GTP – is active), β , and γ.
Gi, Gs, Gq
activates one of 2 enzymes - Phopholipase C OR Adenylyl cyclase (depends on type of NT receptor)
cAMP pathway - in sympathetic can be inhib or excitatory
deals with PROTEIN Phosphorylation (not calcium as in phospholipase c)
in parasympathetic ONLY inhibitory (decreasing protein phosphoylation)
phopholipase C - to DAG, IP3
activates CALCIUM BINDING
DAG uses protein kinase C
IP3 creates CA2+ rleases - ACTIVATES CALCIUM BINDING PROTEINS
Muscle sources of energy - ATP, phosphoCREATINE, glycolysis, oxidative metabolism (carbs first 2 - 4 hours - then fats) 95% energy from this
ATP - lasts for 1 - 2 seconds
ATP + phosphCREATINE - 5 - 8 seconds
glycolosis can sustain for 1 minute
glycolysis can occur w/o oxygen
and makes MORE - 2.5
glycolosis of glycogen (liberates energy to create ATP from ADP via breaking down glycogen to pyruvic acid and lactic acid)
max muscle efficiency?
moderate velocity is best for efficiency
when veloticity is 30% of max
will lose a lot to heat, friction (if contraction too rapid
if no work performed - m not move but is contracting - wasting energy
isometric - m not shorten during contraction
isotonic does shorten but tension remains constant
The active length-tension relationship
is thought to occur as a result of the degree of overlap between the actin and myosin filaments within an individual sarcomere
The length (preload) at which the fiber generates the most active tension is called the optimal length (Lo)
The active tension
is maximal when there is maximal overlap of thick and thin filaments and maximal possible cross-bridges.
The increase in the force of contraction of skeletal muscle is regulated by
the number of motor units recruited by the central nervous system (CNS) and by their frequency of activation
The velocity of shortening
reflects the speed of cross-bridge cycling, determined by the muscle’s ATPase activity.
The velocity of shortening will be maximal (Vmax) when the afterload on the muscle is zero.
As the afterload on the muscle increases, the velocity will be decreased because cross-bridges can cycle less rapidly against the higher resistance.
bradyphrenia
slow thinking
bradykinesis
slow moving
vermis
The vermis (pl: vermes) of the cerebellum is an unpaired medial structure which separates the cerebellar hemispheres. The neocerebellar posterior lobes join in the midline behind the primary fissure to separate the vermis into superior and inferior portions.
Dandy–Walker malformation (DWM),
vermis not fully form -> hydrocephalus -> 4th
may see Noncommunicating hydrocephalus and spina bifida associated with Dandy-Walker malformation
also known as Dandy–Walker syndrome (DWS), is a rare congenital brain malformation in which the part joining the two hemispheres of the cerebellum (the cerebellar vermis) does not fully form, and the fourth ventricle and space behind the cerebellum (the posterior fossa) are enlarged .
What are the 3 common causes of noncommunicating hydrocephalus?
Stenosis of the aqueduct of Sylvius, colloid cyst blocking the foramen of Monro, tumor
fibers of corona radiata -
Normal pressure hydrocephalus, in which ventricular distention stretches the fibers of the corona radiata
The corona radiata is a bundle of nerve fibers located in the brain. … The brain stem and the cerebral cortex both are involved in sensation and motor function, and the corona radiata connects both motor and sensory nerve pathways between these structures.
The most prominent projection fibers are the corona radiata, which radiate out from the cortex and then come together in the brain stem. The projection fibers that make up the corona radiata also radiate out of the brain stem via the internal capsule.
A patient takes a drug that stops DNA replication by inhibiting eukaryotic topoisomerase II. What drug is this?
TWO SIDED - Etoposide or teniposide
vs. for topoisomerase I - they are irinotecan/topotecan
I CAN !
antibiotic that inhibits DNA gyrase (prokaryotic topoisomerase II) and topoisomerase IV. Which antibiotic is this?
Fluoroquinolone
Difference between polymerase i vs iii
DNA polymerase 3 is essential for the replication of the leading and the lagging strands whereas DNA polymerase 1 is essential for removing of the RNA primers from the fragments and replacing it with the required nucleotides. These enzymes cannot replace each other as both have different functions to be performed
What eukaryotic enzyme is a reverse transcriptase that adds DNA to the 3’ ends of chromosomes?
Telomerase (RNA-dependent DNA polymerase)
5’ vs 3’ dna
The 5’ and 3’ mean “five prime” and “three prime”, which indicate the carbon numbers in the DNA’s sugar backbone. The 5’ carbon has a phosphate group attached to it and the 3’ carbon a hydroxyl (-OH) group. This asymmetry gives a DNA strand a “direction”.
apurinic or apyrimidinic site WITHOUT
In base excision repair, what do the apurinic/apyrimidinic endonucleases do?
GEL PLease
They nick the 5′ end of the apurinic or apyrimidinic site
an AP site (apurinic/apyrimidinic site), also known as an abasic site, is a location in DNA (also in RNA but much less likely) that has neither a purine nor a pyrimidine base, either spontaneously or due to DNA damage.
In single-strand DNA repair, in what phases of the cycle do nucleotide excision repair, base excision repair, and mismatch repair occur?
nucleotide G1
base excision - thru out - it’s BASICally always happening
miSSSSSmatch - Synthesis
A process uses intact dsDNA as a template to repair damaged DNA without losing nucleotides. In what diseases is this repair process defective?
dsDNA = DOUBLE STRANDED DNA
Fanconi anemia and ovarian and breast cancers with BRCA1 mutation (process is homologous recombination)
A patient has autoantibodies against glomerular basement membrane. What type of collagen is most likely being targeted?
GoodPasture’s type IV
Hypersensitivity Type II
GoodPastures,
Myathenias Gravis
neural crest ?
Albinism = problem with melanocytes, deficiency in melanocytes. Defect in tyrosinase, which is unable to convert tyrosine to melanin.
Ectoderm = Skin, CNS
Endoderm = including gut epithelium, pancreas, liver, lungs
Mesoderm = Muscle, bones, connective tissue
Non-neural crest neuroectoderm = Brain and spinal cord
motor deficits of the lower extremities
(spina bifida and tethered cord)
developmental disorders, which affect the cerebral cortex and other regions of the brain
(meningomyelocele and anencephaly),
enlarged cranium, cerebellar damage, headaches, vomiting, an inabilityto learn and maintain acquisition of motor skills, and lack of coordination of the trunk
dandy walker
neural crest cells fail to migrate properly. will effect?
a. Chromaffin cells b. Dorsal root ganglion c. Autonomic ganglion cells d. Schwann cells
cells developing from the walls of the neural tube that include the alar, basal, and floor plates have no relationship with neural crest cells. The ventral horn cells are derived from the basal plate.
Anencephaly
calvaria - open skull
is the failure of the rostral neuropore to close, resulting in open calvaria.
Lissencephaly
absence of normal cerebral convolutions and a poorly formed sylvian fissure.
spina bifida - vitamin problem - anemia
In adult = megaloblastic anemia = large immature blood cells
Dermatitis = pellagra B3 deficiency
Night blindness = vitamin A deficiency
Numbness and tingling in the extremities can be seen in B12 deficiency
Poor wound healing = vitamin C
primary vs secondary neuralation
Open NTDs usually result from defective primary neurulation, whereas closed NTDs are the result of defective secondary neurulation.
OPEN - a-fetoprotein UP
closed - spina bifida oculta
In primary neurulation, the neural plate creases inward until the edges come in contact and fuse. In secondary neurulation, the tube forms by hollowing out of the interior of a solid precursor.
drugs that inhibit folic acid
valproic acid and methotrexate.
some medications reduce or inhibit production of folic acid, including valproic acid and methotrexate.
The extent of neural involvement progresses with the different forms of spina bifida cystica;
skin sensation is usually lost from the affected region, and there is some degree of muscle paralysis, particularly with meningomyelocele and myeloschisis. Meningocele does not always cause nerve damage.
fetal alcohol syndrome
leading cause of congenital malformations in the United States.
are relatively small eyes with narrow, sometimes drooping eyelids and small palpebral fissures; as well as a smooth philtrum and a vermillion border on the thin upper lip. In addition limb dislocations, intellectual disability, and heart defects may occur with this syndrome.
Syringomyelia
associated with a type 1 Chiari malformation
Type 1 Chiari malformation leads to a downward herniation of the cerebellar tonsils into the foramen magnum, which can manifest with headaches, as seen in this patient. Acquired causes of syringomyelia include trauma, whiplash injury in the elderly, tumor, and inflammation.
enlargement of the central canal of the spinal cord, most commonly occurring at C8-T1. Crossing fibers of the spinothalamic tract are damaged (causing loss of pain and temperature sensation), but dorsal column function is preserved (intact position and vibration sense).
Communicating hydrocephalus
is caused by impaired absorption of cerebrospinal fluid in the absence of any flow obstruction between the ventricles and subarachnoid space. It is typically associated with malfunctioning arachnoid villi.
Congenital aqueductal stenosis
is a common cause of congenital hydrocephalus, manifesting very early in life with symptoms of increased intracranial pressure, such as vomiting, altered mental status, and papilledema.
Dandy-Walker syndrome
Drugs may cause - warfarin, retinoic acid
a group of malformations reflecting disruptions in the development of the brainstem and cerebellum, probably related to the migration of the hombic lip. The term is generally applied to malformations showing a triad of changes: (1) partial or complete agenesis of the cerebellar vermis, with anterior rotation; (2) dilation of the fourth ventricle; and (3) enlarged posterior fossa with superior displacement of the tentorium. Most cases are diagnosed within the first year, but less severe cases may not be recognized until childhood or, occasionally, adulthood.
The correct answer is: Enlarged fourth ventricle and absent cerebellar vermis
is a congenital noncommunicating hydrocephalus typically associated with a cluster of abnormal findings that include abnormal formation of the cerebellar vermis.
Lateral medullary syndrome, or Wallenberg syndrome,
usually occurs as a result of occlusion of one of the posteroinferiorcerebellar arteries (PICA). It manifests with loss of pain and temperature sensations over the contralateral side of the body and the ipsilateral face, along with vertigo, dysarthria, dysphagia, and Horner’s syndrome.
Lissencephaly,
should have 6 cortical layers
here reduced to four
meaning “smooth brain, “ refers to a defect in neuronal migration that yields an agyric cerebral cortex in which the normal six neocortical layers have been reduced to four, as seen in this coronal section.
A fasciculation, or muscle twitch,
is a spontaneous, involuntary muscle contraction and relaxation, involving fine muscle fibers. They are common, with as much as 70% of people experiencing them. They can be benign, or associated with more serious conditions.
Syringomyelia,
a cyst or cavitation of the central canal of the spinal cord forms. It is moe common at the cervical level as seen in this case, but lumbar cysts are possible. It can follow many types of injury, including those resulting from meningitis or from trauma. Many cases are associated with a congenital Chiari type I malformation, in which the inferior cerebellum becomes displaced downward. Because the cyst begins centrally, the axons of the anterior white commissure of the spinal cord are destroyed, resulting in segmental loss of pain and temperature. If the cavitation extends anterolaterally, it may destroy lower motor neurons causing the observed weakness and fasciculations.
notocord creates?
and neural ectoderm (D 18-21)
a PLATE - on the plate is a CREST toothpaste TUBE
neural crest, neural tube
A fetus’s myelencephalon fails to develop. Communication of the brain with what more caudal structure will likely be affected?
The spinal cord, which is immediately caudal to the medulla (the derivative of the myelencephalon)
To which 4 cell types does the neuroepithelia give rise?
CNS neurons, ependymal cells, oligodendroglia, astrocytes
Which 2 types of cells in the nervous system are derived from the neural crest?
Schwann cells and peripheral nervous system neurons
The peripheral nervous system (PNS), which consists of the neurons and parts of neurons found outside of the CNS, includes sensory neurons and motor neurons. Sensory neurons bring signals into the CNS, and motor neurons carry signals out of the CNS.
A pt who recently had a stroke has reactive gliosis around the infarct. What is the embryologic origin of the cell type involved?
Neuroepithelia, which gives rise to astrocytes that proliferate in reactive gliosis (astrocytosis)
Spina bifida occulta,
a defect in the bony vertebral column with no myelomeningocele herniation
Symptoms of spina bifida occulta
back pain. leg weakness. pain in the back of the legs. loss of bladder or bowel control. scoliosis, or a curving of the spine. numbness in the back or legs. misshapen legs and feet.
An infant has cyclopia, holoprosencephaly, and a midline proboscis. What genetic pathway causes this finding?
What midline defect is associated with a mild or moderate mutation in the sonic hedgehog pathway?
The sonic hedgehog (SHH) signaling pathway, also associated with holoprosencephaly
Cleft lip and/or palate
An infant has a monoventricle with fused basal ganglia on MRI. What 2 syndromes are associated with these findings?
Trisomy 13 and fetal alcohol syndrome (this is holoprosencephaly)
An infant with hydrocephalus and herniation of the cerebellar vermis can’t move her legs. What is the most likely Dx?
Chiari II malformation with associated lumbosacral meningomyelocele causing weakness/sensory loss at levels below the lesion
A newborn is diagnosed with a Dandy-Walker malformation. How do you characterize this defect?
The cerebellar tentorium or tentorium cerebelli (Latin for “tent of the cerebellum”) is an extension of the dura mater that separates the cerebellum from the inferior portion of the occipital lobes.
The cerebellar vermis is missing which leads to cystic dilation of the 4th ventricle filling the enlarged posterior fossa
The relationship of Arnold-Chiari and Dandy-Walker malformations. ✓ The posterior fossa is abnormally small in cases of Arnold-Chiari malformation because the tentorium is too low, whereas it is abnormally large in the Dandy-Walker malformation because the tentorium is too high.
pseudo-unipolar neurons
nodose (vagus nerves) and petrosal (glossopharyngeal nerves) ganglia terminate in the vascular walls of the carotid sinus and aortic arch and sense blood pressure changes.
and DORSAL ROOT ganglia
In pseudo-unipolar neurons, a single axon arising from the cell body divides into two branches. One of the branches terminates as fine endings that serve as peripheral receptors, whereas the other branch terminates on neurons in the central nervous system (CNS). The peripheral nerve endings of the pseudo-unipolar neurons located in the nodose (vagus nerves) and petrosal (glossopharyngeal nerves) ganglia terminate in the vascular walls of the carotid sinus and aortic arch and sense blood pressure changes. Signals received from the vascular nerve endings are transmitted to the CNS for making appropriate adjustment in the systemic blood pressure. Other pseudo-unipolar neurons lie in the dorsal root ganglia
Protein synthesis occurs
in the cell body, the Barr body represents an X chromosome, Nissl substance consists of RNA, and the axoplasm does not contain Nissl substance or a Golgi apparatus.
Astrocytes - glial scar, BBB, cell structure
Astrocytes are a class of glial cells that provide structural support to the brain parenchyma. Days to weeks after cerebral infarction, astrocytes are activated and extend processes to surround the area of liquefactive necrosis, forming a glial scar. This phenomenon is known as gliosis and is analogous to the role of fibroblasts in walling off an abscess. Unlike fibroblasts, however, astrocytes do not secrete collagen, and it is the cytoplasmic processes themselves that provide structural support. Astrocytes are also involved in potassium metabolism and maintain the blood-brain barrier. They are the primary repair and support cells of the central nervous system (CNS), and they stain for glial fibrillary acidic protein (GFAP).
Here are the cells responsible for the other functions listed:
