module 1 Flashcards
what is the resting membrane potential
the constant voltage across the membrane when the cell is at rest
what is the synaptic potential
a change in potential when neurotransmitters bind to a receptor that allows ions to flow across the neuronal membrane
what is an action potential
a nerve impulse or spike that travels along an axon
what are the two requirements for generating voltage difference across the cell membrane
concentration gradient
membrane is selectively permeable
how do ions move relative to the concentration gradient
from high to low concentration by diffusion
how are membranes selectively permeable
because there are ion channel proteins
what is the equilibrium potential
the force of diffusion is equal and opposite to the electrical force
- net movement of ions is zero
(does not look at number of ions)
what does the nernst equation describe
ionic flow based on electrochemical gradients
what does the GHK equation predict
the resting membrane potential (Vm) of a cell for multiple ions present in a cell
what is the relative permeability of an ion
the ease with which the ions moves across the membrane
at rest, what kind of channels can remain open and allow ions to diffuse in and out of the cell
leak channels (not gated)
what ion leaks out more than others
potassium
what is active to counter the leak of potassium ions
sodium-potassium ATPase pump
what is moved in and out of the cell with the Na-K ATPase pump
3 Na+ out
2 K+ in
why is ATP required for the Na-K pump
because the ions are moved against their gradient
what concentrations are kept stable because of the Na-K pump
ionic concentrations
what chloride transporter do immature neurons express
NKCC1
what does NKCC1 do
pumps chloride into neurons so immature neurons have a high concentration of chloride inside the cell and a low concentration of chloride outside the cell
how does the NKCC1 transporter depolarize the cell in immature neurons
GABA-A receptors open in response to binding of GABA which allows chlorine ions to flow down their concentration gradient from inside to outside the cell, which creates a more positive inside of the cell as negative ions leave, depolarizing it
does the NKCC1 transporter depolarize or hyperpolarize the cell
depolarize
easier to fire AP
what chloride transporter do mature neurons express
KCC2
what does KCC2 do
pumps chloride out of neurons so mature neurons have a low concentration of chloride inside the cell and a high concentration of chloride outside the cell
how does the NKCC2 transporter hyperpolarize the cell in mature neurons
GABA-A receptors open in response to binding of GABA which allows chlorine ions to flow down their concentration gradient from outside to inside the cell, which creates a more negative inside of the cell as negative ions flow in, hyperpolarizing it
does the NKCC2 transporter depolarize or hyperpolarize the cell
hyperpolarize
harder to fire AP
in an AP are voltage gated channels open or closed at rest
closed
in an AP what causes the cell to depolarize
AMPA receptors open and sodium ions flow in
in an AP what is the threshold voltage
the voltage at which voltage-gated sodium channels open
in an AP what happens when the cell reaches threshold voltage
sodium channels open and sodium ions flow into the cell to depolarize the cell to positive voltages
in an AP at positive potentials are sodium channels activated or inactivated
inactivate by the channel being blocked and ions not being allowed to flow through
what is the absolute refractory period in an AP
sodium channels are inactivated and cells cannot fire another action potential until the channels recover from inactivation
in an AP when are potassium channels activated
top of the curve when cell is at positive potentials
in an AP what happens when potassium channels are activated
potassium ions flow out of the cell and the inside of the cell becomes less negative, hyperpolarization
in an AP what is the relative refractory period
potassium ions continue to flow in and the membrane voltage can be more negative than the resting potential
AP can be fired if input is larger (bigger depolarization than original required)
do AP move forward or backward
AP can only move forward not backward
what are three roles of refractory periods
- limit the number of APs that a neuron can produce per unit time
- prevent re-excitation of the same membrane segment that was just excited
- prevents APs from propagating backward to their point of initiation
why cannot passive current flow conduction along an axon be used to transfer information over long distances
passive current flow along an axon decays with distance
what is the difference between passive and active current flow
active current flow along an axon shows a constant amplitude of the action potential assuming equal distribution of channels along the axon so it does not decay with distance
what is difference about the sodium channels in the nodes of ranvier
there are more of them
what is the role of myelin
increases conduction velocity
how do AP travel through nodes of ranvier
AP travels passively to the next node where it is regenerated (called saltatory conduction)
what does myelin do to the strength of an AP
maintains the strength of the impulse message as it travels down the axon
how does myelin provide protective insulation
due to its fatty protein coating
the brain and spinal cord contain 50% white matter that is made up of what
oligodendrocytes
how many axons does one oligodendrocyte wrap around
many
what anchors the layers of myelin together in the CNS
myelin basic protein (MBP)
proteolytic protein (PLP)
what are motor and sensory peripheral nerves myelinated by
schwann cells
how many axons does one schwann cell wrap around
a single peripheral axon
what is the relation between nodes of ranvier and schwann cells
each segment between nodes of ranvier is wrapped by a different schwann cell
how many schwann cells are needed to myelinate one long axon
multiple
what does blocking potassium channels do to AP
prolongs the AP because the cell is not able to repolarize and takes much longer to come back to resting membrane potential
-relative refractory period is much longer
-neuron needs smaller input to fire
what are the three cells contained in a CNS synapse
presynaptic neuron
astrocyte
postsynaptic neuron
what synaptic vesicles are able to be released
ones at the active zone
(there are many different pools of vesicles)
what is the active zone on a presynaptic end of a synapse
area on the presynaptic membrane where vesicles release occurs
- contains many proteins that participate in various aspects of synaptic vesicle release and recycling
what leads to vesicle fusion and release of NT
voltage dependent calcium channels open in response to depolarization and the inflow of calcium leads to vesicle fusion and release of NT
where are vesicles synthesized
in the soma and then transported to the presynaptic terminal where they are stored
how are vesicles transported to the presynaptic terminal
along microtubules
- motor proteins generate force by coupling ATP hydrolysis to conformational changes
what are microtubules
polymers of tubulin stabilized by tau proteins
what are vesicles tethered to the release sites by
SNARE complex made of synaptobrevin on the vesicle membrane and SNAP 25 and syntaxin on the plasma membrane
what events lead to membrane fusion and release of vesicle contents
calcium binds to synaptotagmin
what are the four types of glial cells
astrocytes
oligodendrocytes
schwann cells
microglial cells
what are the functions of astrocytes
only found in CNS
maintain chemical environment around neurons
end-feet surround capillaries and help form the BBB
what are the functions of oligodendrocytes
make myelin in the CNS
what are the functions of schwann cells
make myelin in the PNS
-important in regeneration of PNS neurons
what are the function of microglial cells
hematopoietic cells and like macrophages
scavenge and secrete cytokines at site of injury
number of microglia increases in injury
what is the role of astrocytes at synapses in the CNS
astrocyte secreted factors control different aspects of synaptic development and maturation
what do synapse-astrocyte interactions contribute to
synaptic plasticity
what do astrocytes do to neurotransmitters
remove neurotransmitters from synaptic cleft and stop communication
what kind of homeostasis are astrocytes essential for
ionic homeostasis
potassium and calcium balance
what are the three ways that neurotransmitters can be removed from the synaptic cleft
destruction by enzymes
reuptake by presynaptic neurons
removal by transporters on astrocytes surrounding the synapse
what enzyme is acetylcholine destroyed by in the synapse
acetylcholine esterase
what four NT have transporters embedded in the presynaptic membrane
serotonin
dopamine
NE
epi
what transporters transport glutamate to astrocytes to be converted to glutamine
excitatory amino acid transporters (EAAT) that are present on astrocytes
how is the action of glutamate released into the synaptic cleft terminated
by uptake into surrounding glial cells via EAATs
within glial cells, what converts glutamate to glutamine
glutamine synthetase
glutamine is taken up into nerve terminals and converted back to glutamate by
glutaminase
how is glutamate loaded into synaptic vesicles
via vesicular glutamate transporters (VGLUTs)
is removal of glutamate from the synapse slow or rapid
rapid
what do dendritic spines provide
compartmentalization
- large head connected by very thin neck serves to compartmentalize molecules to individual synapses
what kind of synapses do dual spines have
both excitatory and inhibitory
T or F: activation of one synapse can be selectively strengthened without influencing neighboring synapses
true
what does the dendritic spine neck do to resistance and kinetics of the cell
increases resistance and can change the kinetics of voltage change that is transmitted to the soma
when will extra-synaptic receptors have a response
only if NT spills out of synapse
can synapses on dendritic spines modulate each other
yes
synapses on the shaft of dendrites can modulate response from many upstream spines
what clusters receptors near signaling molecules
postsynaptic proteins form a scaffold
what four things are contained at a glutamate synapse postsynaptic density
receptors
scaffolding proteins (PSD 95, Homer, Shank)
signaling molecules (CamKinase II)
actin filaments
what is PSD important for
scaffolding protein that is important for signaling as well as holding the shape of spines
what causes summation of AP
convergence of hundreds or thousands of presynaptic inputs across the soma and dendritic spines leads to summation
as a result of summation across space and time, what does the membrane potential depend on
whether it reaches threshold
what are the two types of NT receptors
ionotropic
metabotropic
what type of receptors are GPCRs
metabotropic
- cascade of phosphorylation events and second messenger production
- slow
what is it called when the receptor itself is also the ion channel
ionotropic receptors
- fast
can G proteins bind to and activate ion channels
yes
what are three types of heterotrimeric G proteins
Gs
Gi
Gq
are AMPA receptors fast or slow and what ions do they flux
fast kinetics
flux only sodium ions
are NMDA receptors fast or slow and what ions do they flux
slow
flux both sodium and calcium ions
what are two types of ionotropic receptors
AMPA
NMDA
what are the steps in glutamate signaling
- glutamate released from presynaptic terminal
- NMDA receptors activated
- depolarization of postsynaptic terminal
- magnesium repelled from the pore of the channel
- NMDA receptor can flux calcium and sodium
what are two stores of calcium
flux through ligand gated or voltage gated ion channels
release from intracellular calcium stores (in ER and mitochondria)
what two ion channels releases calcium from intracellular stores
IP3 receptors
ryanodine receptors
what are two examples of effector proteins that calcium can affect
calmodulin
cam kinase II
what are four ways calcium can be brought down to normal levels
pumping it out of the cell by calcium pump using ATP
Na/Ca exchanger that transports Na in and Ca out
Ca pump on ER membrane that pumps Ca into intracellular stores and transports Ca into the mitochondria
binding by buffering proteins like calbindin
what are proteins phosphorylated by
protein kinases
what are proteins dephosphorylated by
protein phosphatases
what are the two layers of the dura mater
one layer that is fused with the skill
one layer that is fused to the arachnoid
is there space between the two layers of the dura mater
no except where they separate to form sinuses (sinuses filled with CSF)
which meninge layer has pain receptors
dura mater
does the arachnoid mater follow the inner layer of dura into the sulci
no
- results in a large space filled with CSF
what is the subarachnoid space
space between the arachnoid and pia mater that is filled with CSF and contains blood vessels and arachnoid trabeculae
what is the arachnoid trabeculae
made of cells and collagen and holds arachnoid and pia together as well as blood vessels
what do arachnoid granulations do
allow CSF to exit the subarachnoid space and enter the sinuses to eventually enter the bloodstream
(takes things out of the brain and back into circulation)
what is the pia mater
closely follows the surface of the brain and adheres to glia on the surface of the brain
what are the three meninge layers
dura, arachnoid, pia
what type of molecule can cross the BBB
hydrophobic molecules because BBB is a phospholipid bilayer
what are the capillaries in the CNS linked by
tight junctions
what are endothelial cells in the CNS surrounded by
pericytes and the basement membrane
what surrounds blood vessels in the CNS
astrocytic feet
can macrophages squeeze out of capillaries in the CNS
no because of the presence of tight junctions
how do astrocytes modulate blood flow
- mGlu receptors activate on the astrocyte surrounding the synapse
- intracellular Ca in astrocytes increases
- PLP (Ca dependent 2nd messenger) is activated and diffuses through the astrocytes
- PLP activates formation/release of prostaglandins and vasoactive compounds
- blood vessels respond by dilating
- blood flow to the area increases
what are two roles of astrocytes at the synapse
- removal of glutamate from the synaptic cleft
- ionic homeostasis (especially of K)
where is anterior circulation derived from
internal carotid artery
where is posterior circulation derived from
vertebral artery
what connects blood vessels from the L and R side of the brain
circle of willis
what does the circle of willis create
a redundant blood supply because it is a continuous structure connecting the blood vessels
what areas of the brain does the middle cerebral artery supply (MCA)
language areas, sensory and motor areas, cognition
(basal ganglia, cortex, lobes, midbrain)
what areas of the brain does the anterior cerebral artery supply (ACA)
frontal cortex
cognitive areas, sensory areas in frontal lobe
what areas of the brain does the posterior cerebral artery supply (PCA)
vision, thalamus related
mid brain, brain stem, occipital lobe
what parts of the brain does the basilar artery supply
pons, lower midbrain, thalamus, hypothalamus
how are sinuses formed
separation of layer of dura
where does the CSF from the sinuses eventually drain into
jugular vein
what do arachnoid granulations act as
one way valves for CSF to flow from brain tissues to sinuses
where is CSF produced
choroid plexus present in each of the four ventricles
what happens as CSF passes from the arterial perivascular space through the substance of the brain
metabolic wastes and discarded proteins are rinsed into the perivascular spaces surrounding veins and perivascular fluid flows into the subarachnoid space/sinuses
when does convective flow of CSF and interstitial fluid increase
during sleep when extracellular spaces expand
how is blood supplied to the spinal cord
branches of aorta that form the vertebral and spinal arteries
what are the highly vascularized areas of the brain whose capillaries do not contain the tight junctions of the BBB but instead are fenestrated (gap between endothelial cells)
circumventricular organs
(allows free exchange of molecules between blood and nervous tissue)
what are the sensory areas of the circumventricular organs called
subfornical region
OVLT
area postrema
what are the sensory areas of the circumventricular organs involved in
homeostatic functions like fluid/blood pressure balance, temperature, respiration, hunger (glucose levels)
what are the secretory areas of the circumventricular organs called
pineal gland
median eminence
intermediate pituitary
posterior pituitary
what are the secretory areas of the circumventricular organs involved in
neurosecretion of secrete hormones prolactin, growth hormones, oxytocin, feedback loops from rest of body
when do surface electrodes of an EEG register a signal
when cells signal in synchrony
what can ERP (event related potentials) be recorded from
EEG
how do CT scans work
short pulses of narrow x-ray beam while detectors are placed across the brain that probe small portions of the tissue
radiodensity calculated at each point and complete image is generated
how are images for a CT scan collected
as slices
what is a drawback of a CT scan
high level of radiation
what is PET imaging based on
the use of specific metabolites by active cells
how does PET imaging work
- isotope of glucose injected by IV
- isotope accumulated in active neurons but cannot be metabolized
- as isotope decays, two positrons are emitted and travel in opposite directions
- gamma rays are produced
- positrons detected when they react with electrons
- positrons mapped onto a CT or MRI image
what kind of diseases are PET scans used for
neurodegenerative diseases
how does MRI imaging work
- protons lineup with magnetic field and will spin at a frequency that depends on the field strength
- when a brief radiofrequency pulse is applied, atoms are knocked out of alignment
- protons emit energy as they realign themselves with the magnetic field
(no radioactive substance injected although a contrast is sometimes used)
what are T1 weighted MRI images
produced by using a short time between successive radio frequency pulses
- grey matter appears darker than white matter
what are T2 weighted MRI images
produced with a longer time in between successive radio frequency pulses
- white matter appears darker than gray matter
- signal of water is enhanced
how does fMRI work
depends on hemoglobin molecule distorting the magnetic properties of hydrogen
- distortion depends on whether oxygen is bound to hemoglobin or not
is the resolution of a fMRI better than a PET scan
better
what is diffusion tensor imaging (DTI)
type of MRI that allows visualization of fibrous structures like large tracts of white matter
what kind of disease is DTI useful for
multiple sclerosis
what is a magnetoencephalography (MEG)
records the magnetic consequences of the brains electrical activity
- temporal resolution is milliseconds
what is magnetic source imaging (MSI)
combines structural MRI with MEG
what kind of scan has the highest anatomical resolution
fMRI
(can detect very small structures)
what kind of scan has the highest sensitivity
PET
(can detect very low signals)
what is the sensitivity and temporal resolution for a PET scan
highest sensitivity
low temporal resolution
what is the spatial and temporal resolution for a EEG
low spatial resolution
high temporal resolution
what is the sensitivity and spatial resolution for a MRI
good spatial resolution and sensitivity
what is the spatial and temporal resolution for a fMRI
good spatial resolution
good temporal resolution
what will symptoms of a stroke depend on
the artery that is blocked/hemorrhaging
what is the most significant risk factor for a stroke
hypertension
what is a CVA
cerebrovascular incidence (CVA) is a stroke
- occurs when there is obstruction of blood flow
what is a TIA
transient ischemic attack (TIA)
- sxs last less than 24 hours
what is the difference between a TIA and a stroke
a stroke has symptoms that last for more than 24 hours
what are the two main categories of strokes
ischemic strokes: caused by blockage of an artery
hemorrhagic strokes: caused by bleeding
what is an ischemic stroke
occurs when a blood vessel that supplies the brain becomes blocked or clogged and impairs blood flow to that part of the brain
- brain cells and tissues begin to die within minutes forming a cerebral infarct
what are the two types of ischemic strokes
thrombotic strokes: caused by a blood clot that develops in blood vessels inside the brain
embolic stroke: caused by a blood clot/plaque debris that develops elsewhere in the body and then travels to one of the blood vessels in the brain through the bloodstream
what is a global ischemic stroke
caused by global decrease in blood due to cardiac arrest, valvular heart disease, or lowered blood pressure
what is a hemorrhagic stroke
occurs when a blood vessel ruptures and bleeds
- cells/tissues do not get oxygen and nutrients
- pressure builds in surrounding tissues and irritation and swelling occur
what are the two categories of hemorrhagic stroke
intracerebral hemorrhage: bleeding from blood vessels in brain
subarachnoid hemorrhage: bleeding in subarachnoid space, most commonly as result of bleeding aneurysm
what are four things that can cause hemorrhagic strokes
chronic hypertension
congenital aneurysm/AVM
TBI
cocaine/amphetamine
how does blood accumulate in the meninges to form a hemotoma
rupture of blood vessels
where is an epidural hematoma and what is it caused by
blood between skull and dura that has peeled off
due to injury
where is a subdural hematoma and when is it common
blood between dura and the brain
common in old age
what causes cerebral edema after a stroke
large influx of CSF may drive swelling
- depolarization of injured and swollen tissue is also seen
what is a severe complication of an acute ischemic stroke
cerebral edema
during ischemia, why does excessive fluid accumulate in the intracellular or extracellular spaces of the brain
failure of energy-dependent ion transport
destruction of BBB
what is the treatment for edema that cannot be treated with medication
decompressive craniectomy
what is atherosclerosis
narrowing of blood vessels due to accumulation of plaques
- reduces blood flow especially in small end-capillaries
what do plaques have high levels of
calcium, fatty acids, triglycerides, cholesterol
what are plaques covered by
a fibrous cap of collagen that is typically weak and prone to rupture
what does the cap of a plaque form if it enters the bloodstream
thrombus
where is a thrombus most likely to block blood flow
branch points and atherosclerotic capillaries
how is the clotting cascade activated
by collagen or injury to blood vessels
what is the order of the clotting cascade
activation of thrombin
–> thrombin catalyzes conversion of fibrinogen to fibrin
–> fibrin forms crosslinks to form a clot
what do blood clots contain
meshwork of platelets covered by crosslinked fibrin
atherosclerosis combined with hypertension increases what risk
risk of stroke
what is a medication that helps prevent platelet aggregation and is prescribed to patients at risk of stroke
NSAIDs (non steroidal anti inflammatory drugs)
what medications prevent fibrin from forming
heparin and coumadin (blood thinners)
can the core of the infarct be rescued after the fact
no, the cells are dead
what is the penumbra
cells surrounding the primary lesion of the stroke
can the penumbra be recovered after the fact
it is possible to limit stroke damage with quick reperfusion because restoring blood supply to the penumbra can help unhealthy cells recover and limit stroke injury to the core
what two important metabolites does the blood carry for the brain
glucose and oxygen
how does the brain use ATP
for the Na/K pump to maintain ion gradients
vesicular release and recycling at presynaptic terminals
what does constant synthesis of ATP require
both glucose and oxygen
what kind of cellular respiration can neurons perform
aerobic cellular respiration (with oxygen)
- need constant oxygen for oxidative phosphorylation
does brain tissue store glucose
no
- also lacks ability to break down fatty acids
why does the brain need a constant supply of glucose and oxygen
- the brain cannot store glucose in any form that is able to be broken down when the brain needs it
- neurons can only do aerobic respiration (no anaerobic)
what is the only way neurons can get ATP
breakdown of glucose using aerobic cellular respiration
what happens to the brain in relation to glutamate when there is no ATP
excitotoxicity
- astrocytes usually take up glutamate from synapse but without ATP they cannot so glutamate leaks out of the synapse to keep exciting neurons
what happens to cell death signaling when there is no ATP
cell death increases
what happens to the brain in relation to mitochondria when there is no ATP
mitochondrial dysfunction leads to the production of reactive oxygen species which will make proteins misfold/kill everything they encounter
why does inflammation occur when there is no ATP in the brain
when the BBB breaks down, immune cells cross the BBB and cause neuroinflammation
what are the differences between necrosis and apoptosis
necrosis:
passive, uncontrolled, and accidental cell death
cell bursts, contents released, microglia come to clean up contents, INFLAMMATION
apoptosis:
programmed cell death
tightly regulated active ATP-dependent process, forms vesicles for microglia to clean up, NO INFLAMMATION
how does apoptosis occur
- mitochondria release pro-apoptotic proteins like cytochrome c
- cytochromes activate caspases (enzymes that destroy cellular proteins)
- DNA fragments and membrane integrity is maintained so cellular contents don’t spill out
- apoptotic bodies are cleaned up by macrophages/microglia
what are the most sensitive cells to anoxic injury
neurons
what is liquefactive necrosis
occurs in the brain as many macrophages clean up the necrotic cellular debris
what scan gives the most detail of an ischemic stroke
MRI
how many days after a stroke does the penumbra stay viable
two days
what is the difference between diffusion-weighted images and perfusion images of an MRI
diffusion-weighted images: show structural (permanent) destruction
perfusion images: show areas where the brain has abnormally low perfusion (flow)
what is inserted into the femoral artery to visualize both arteries and veins
contrast media
- can cause stroke, allergic reactions, and cause renal failure
why are blood thinners a treatment for stroke
they block the clotting cascade
what are three stroke treatments
- restore blood flow by removing the clot or stopping the hemorrhage
- protect neurons
- rehabilitation
how can a blood clot be dissolved/lysed
perfusing tissue plasminogen activator (tPA)
what are three treatments for excitotoxicity because of decreased ATP
- glutamate receptor antagonists
- block calcium signals
- bind and remove ROS/NOS
how do neurons in the core of the infarct die
necrosis
how do neurons in the penumbra die
apoptosis
how can hypothermia be used for strokes
reduces cell death, injury, and edema
drawbacks are risk of pneumonia or arrhythmia
how can atherosclerosis be treated
a balloon angioplasty and a stent is placed
why is rehabilitation essential for recovery from a stroke
causes plasticity of neurons, reduction in swelling, dendritic sprouting
what is the critical period after a stroke where rehabilitation is most effective
60-90 days
what do intracellular buffer proteins do when Ca activates them
binds to downstream targets when activated by Ca
what does the calcium pump require in order to pump Ca out of the cell
ATP
what are four things that contribute to the mitochondria’s role in excitotoxicity
- pro-apoptotic proteins on mitochondrial membrane are activated
- cytochrome c –> activation of caspases (enzymes that lead to apoptosis)
- ROS –> membrane lipid breakdown
- increased intracellular calcium
what leads to formation of pores in mitochondrial membranes
hypoxia
in the absence of cellular respiration and lack of ATP, what happens to the mitochondria
they get depolarized
what kind of ischemic strokes are considered focal ischemic strokes
thrombotic strokes
embolic strokes
(global ischemic strokes are not and make up 10% of ischemic strokes)
what is TBI
physical injury to the brain or spinal cord
what scale is used to assess the extent of a traumatic brain injury
glasgow coma scale
what number is worse on the glasgow coma scale
lower number is worse
(does not respond to stimulus is worse than is in extreme pain)
what are the two kinds of injury that TBIs can be divided into
primary injury: injury caused by the initial force
secondary injury: consequences of primary injury
what is the difference between the coup and the counter-coup in a TBI
coup: side of contact; injury will be the same if the head is stationary and hit by moving object or vise versa
counter-coup: rebound effect on the opposite side
what can shear forces of a TBI cause
vascular injury: blood vessels can break and become leaky causing hemorrhage, hematoma, or ischemia downstream of the break or leak
diffuse axonal injury: axons and dendrites break or have leaky membranes causing demyelination, neuronal injury, depolarization, lack of ATP, excitotoxicity
what is reactive gliosis
change in glia after any injury (including stroke)
what are the shear forces in a TBI
forces on axons in the spinal cord or brain which can break
how do astrocytes react to injury
increasing their cytoskeleton and advancing thick processes towards the injury
multiplying
releasing extracellular matrix molecules
what do reactive astrocytes form
a scar that limits inflammation and regulates composition of extracellular fluid
what does brain injury do to glia in relation to regrowth
brain injury elicits responses from activated glia that actively opposes regrowth
what forms the glial scar
overgrowth of the 3 activated glia
- accompanied by a massive influx of immune cells including T-cells, neutrophils, and monocytes
what do scarring astrocytes form around the injury
form a capsule
what is a mature glial scar a barrier to
the regrowth of axons across the site of CNS damage
- also have molecules on their surface that bind to receptors on newly generated axons and inhibit growth
what is axonal sprouting
formation of new processes
- is unsuccessful because of the glial scar
- want to prevent random synapses from forming and working against new formation
what kind of protein deposits are found after a TBI
hyperphosphorylated Tau proteins (like found in alzheimers patients)
what happens to the microtubules when Tau proteins are phosphorylated
microtubules will break because the tau proteins are no longer stabilizing them
are spinal and cranial nerves part of the CNS or PNS
PNS
where is the white matter located in the spinal cord
white matter is outside
- axons are more susceptible to injury
where is the white matter located in the brain
white matter is on the inside, grey matter is on the outside
- neurons are more susceptible to injury
where do sensory axons enter the spinal cord and when do they cross to the other side
enter from skin and pain receptors
immediately decussate (cross over to the contra-lateral side)
where will the loss of pain occur when there is injury to the spinal cord
injury to spinal cord will have contralateral loss of pain
where do motor axons enter the spinal cord and when do they cross to the other side
enter from the motor cortex in the brain and travel to the medulla
decussate in the medulla before entering the spinal cord
where will motor control be lost when there is injury to the spinal cord
injury to the spinal cord will have ipsilateral (same side) loss of motor control
what kind of loss will stroke/brain injury in the corticospinal (motor) tract result in
contralateral loss
injury to the spinal cord will be ipsilateral
decussates in the medulla
what kind of loss will occur with injury to the spinothalamic tract (pain)
contralateral
decussates right away
what kind of loss will occur with injury to the dorsal column (touch)
ipsilateral loss
decussates in the medulla
what can molecules released by oligodendrocytes and astrocytes actively suppress after injury
axonal regeneration
what are the 4 major cellular elements that facilitate peripheral nerve repair
schwann cells
fibroblasts
macrophages
endothelial cells
- all 4 required for formation of a nerve bridge
what are the steps after injury that cause a channel promoting growth to form
injury
immune cells proliferate and invade
demyelination
form a nerve bridge
blood vessels extend into the site
schwann cells proliferate
channel forms that promotes growth
what are three things that are prevented around the injury to protect cells during long term treatment
prevent excitotoxicity
prevent edema
prevent inflammation
how can treatment be used to promote repair after an injury
using artificial biomaterials to promote regeneration in the spinal cord
- stem cells obtained from nasal epithelium and other sources
- drawback: not specific and no control over where progenitor cells end up
what are 3 physical/occupational therapies combined with nerve stimulation that can be used in the long term treatment of brain injury
robot assisted locomotor training
functional electrical stimulation (FES) devices
repetitive transcranial magnetic stimulation (rTMS)
what are 3 experimental therapies being used for brain injuries
masking ligands/receptors that inhibit axonal growth (antibodies against NogoA mask it and prevent its action)
blocking rho (rho collapses the growth cone)
hypothermia
what is the difference between afferent and efferent
afferent: sensory information sent to the CNS (PNS–> CNS)
efferent: motor commands send to the PNS (CNS–>PNS)
what kind of information is somatosensory information
sensory information such as touch, pain, proprioception
what kind of information is visceral sensory information
sensory information that senses physiology like blood pressure
where are neuronal cell bodies located that have modified nerve endings that form touch and pain receptors on the skin
dorsal root ganglia
what is a detmatome
innervation arising from a single dorsal root ganglion and its spinal nerve
how can spinal lesions be localized
by determined which dermatomes are affected
how does pain information get from pain receptors to the somatosensory cortex and other pain centers
- pain and temperature fibers enter the spinal cord
- decussate in the same segment (cross over to the other side of the spinal cord)
- travel to the contralateral somatosensory cortex
what tract are pain and temperature fibers a part of
the anterolateral tract
how does touch information get from touch receptors to the somatosensory cortex
- touch fibers enter the spinal cord
- travel ipsilaterally in the dorsal column
- decussate in the medulla
- go to the contralateral somatosensory cortex
what is the difference between the location of the dorsal columns and the anterolateral tracts
dorsal columns: midline
anterolateral tracts: outer edge of the spinal cord
what pathway do mechanoreceptors and proprioceptors travel to the brain
dorsal column
what pathway do nociceptors and thermoreceptors travel to the brain
spinothalamic tract
/ anterolateral tract
how do motor axons travel from the brain to the spinal cord
as bundles along the pyramidal tract
what is the difference between the lateral corticospinal tract and the anterior corticospinal tract in the efferent motor pathway
lateral: fibers decussate in medulla (90%)
anterior: fiber stay ipsilateral (10%)
what kind of paralysis will a lesion of lateral corticospinal tract result in
ipsilateral paralysis
where will the loss of touch and pain be for a lesion on the left side of the spinal cord
loss of touch on the left
loss of pain on the right
(loss will be below the segment that is lesioned)
what is referred pain
visceral (internal) pain that is perceived at a site different from where it originated
how is referred pain transmitted
via dorsal horn neurons that also convey cutaneous pain
how does visceral pain travel
via the dorsal column
- afferent fibers decussate in the medulla
what nervous system includes the enteric nervous system
autonomic nervous system
what do the axons look like / where are the neurons located in the sympathetic nervous system
chain of sympathetic ganglia runs along the spinal cord
short preganglionic
long postganglionic
what do the axons look like / where are the neurons located in the parasympathetic nervous system
parasympathetic ganglia are close to target organ
long preganglionic
short postganglionic
what is the difference between the direct and consensual pupillary response
direct: bright light is shone, pupillary muscles contract, pupil becomes small
consensual: pupillary muscles of other eye contract at the same time
what is the circuit that is responsible for the pupillary light reflex
- light activates optic nerve
- optic nerve fibers project bilaterally to the pretectum
- pretectum projects bilaterally on the edinger-westphal nucleus
- axons from edinger-westphal nucleus form part of cranial nerve 3 and terminate on ciliary ganglia
- ciliary ganglia have short axons and terminate on pupillary muscle
- constriction of pupils (parasympathetic response)
what is the difference between seizures and epilepsy
seizures: uncontrolled synchronous firing of neurons in brain that cause behavioral abnormalities
epilepsy: clinical syndrome with recurrent, unprovoked unpredictable seizures (usually has underlying cause)
what is the prodromal phase of a seizure
knowing the seizure is on its way
- lightheaded, anxiety, mood changes
what is the aura phase of a seizure
early phase
- odd smell, sound, taste, vision problems
what is the ictal phase of a seizure
time from the first symptom to the end
- intense electrical activity
what is the post ictal phase of a seizure
recovery but physical symptoms are present
what is the best way to diagnose a seizure
EEG
what are focal seizures
start in/on one part or side of the brain and symptoms depend on the focus (what part of the brain it is in)
what is the difference between a seizure with dyscognia and without
with dyscognia: cognitive impairment and often come with aura
what is the difference between a focal and a generalized seizure
generalized seizure involve the entire brain
what are absence seizures
appear as if person is spaced out
what are atonic seizures
loose muscle tone suddenly
what are myoclonic seizures
sudden contraction of a set of muscles (sudden jerky movement)
what are tonic-clonic seizures
contractions of entire body, increased heart rate and BP
what are status epilepticus
seizures last longer than 5 minutes
what are 5 factors that can lead to an epilepsy diagnosis
- epilepsy syndrome: multiple factors that can lead to epilepsy
- idiopathic epilepsy: cause not known
- genetic
- acquired epilepsy: due to head trauma
- drug abuse
what are two main ways to cause repetitive firing of action potentials by a neuron
- shorten absolute refractory period by changing when the Na inactivation protein blocks the channel
- shorten the relative refractory period by causing K+ channels to not hyperpolarize the cell as much
what is a quantum
neurotransmitter contained in one vesicle
where on the neuron is it decided if the potential is enough to cause an AP
at the axon hillock
- EPSP and IPSPs can cancel each other out as long as the potential at the axon hillock is enough to cause the AP to fire
what are basket cells
interneurons that contribute to the negative feedback loop
what are pyramidal cells connected by
gap junctions - forming electrical synapses
- one firing will lead to another firing because they are electrically connected (rhythmic pacemaker cells)
what are mossy fibers
axons of granule cells that project to CA3 pyramidal neurons, neurons in the hilus, and interneurons
what do mossy fibers do in some epilepsy
sprout new fibers and make more connections
what is epileptogenesis
period of structural and functional changes when symptoms are still absent
where in the brain does mesial temporal lobe epilepsy (MTLE) cause damage
hippocampus
why are children more prone to epilepsy
because they have immature neurons that express NKCC1 so there is higher Cl- inside cell, making it easier to excite the cell since it is already depolarized
what are three main categories of drugs used as treatment for epilepsy
enhance GABA action
Na2+ channel blockers
Ca2+ channel blockers
