Neuroscience Flashcards
Describe the early development of the CNS.
- proliferation of the ectoderm in the dorsal midline of the embryonic disc - this forms the NEURAL PLATE
- as the plate thickens further it starts to fold up on the sides
- eventually, the two neural folds fuse dorsally to form a tube (lined by NEUROEPITHELIUM, in which the space in the middle is called the NEURAL CANAL
- at the tip of the neural fold you get little bunches of cells called NEURAL CRESTS, these crests separate form the tube and lie unfused alongside them
- at the other end of the process the neural tube lies in the midline, dorsally to the embryo, on the other side there are two strips of neural crest tissue
State what the neural tube and neural crest go on to become.
- Neural Tube = CNS cells
- Neural Crest = PNS cells
State the 3 cell types the arise from neuroepithelium
- neuroblasts 2. glioblasts 3. ependymal cells
Describe neuroblasts.
- precursors for all neurones that have their cell bodies within the CNS
Describe glioblasts
- become neuroglia -> astrocytes, oligodendrocytes etc
Describe ependymal cells.
- lining of ventricles and central canal - remain close to the inner membrane of the neural tube and they spread out and form a lining around the developing ventricular system
State the differentiation of neural crest cells.
- sensory neurones of dorsal root ganglia and cranial ganglia
- post-ganglionic autonomic neurones
- schwann cells
- non-neuronal derivatives
Explain the layout of neuroepithelium.
- almost all cells are attached to BOTH the inner and outer membranes - it’s just that the nuclei are in different positions
- the cross-section shows fat cells going through mitosis at the bottom
Describe the differentiation of neuroepithelium.
- cells withdraw from the outer membrane towards the inner membrane and go through mitosis
- one of the daughter cells will stay attached to the inner cell membrane, it gets bigger and goes into the cell cycle again
- the other daughter cell migrates away from the inner membrane and then develops into neuroblasts
- they develop processes (one will become the axon) and these axons are directed away from the inner membrane again, as the above occurs over and over you end up with THREE layers
- there is one layer by the inner membrane where you get mitosis occurring, another layer where you mainly have cell bodies and another that has mainly axons -> this is the beginning of the difference between grey and white matter
What controls the process of differntiation and migration?
- signalling molecules (sonic hedgehog), secreted by surrounding tissues, interact with receptors on neuroblasts
- control migration & axonal growth by attraction and repulsion
- depends on concentration gradient and timing
Describe the developing spinal cord.
o 2 significant features:
- > neural canal is even smaller compared to the thickness of the wall
- > grey matter has split into TWO different types: -> alar plate - dorsal and basal plate - ventral
o interneurons in the alar plates are becoming specialised to receive sensory information -> information comes from the developing dorsal root ganglia that developed from the neural crest
in the basal plate there are some interneurons and the development of motor neurones -> means the basal plate has a motor function -> the axons leave the spinal cord to go towards muscles
Describe the anatomy of a mature spinal cord compared to a developing spinal cord.
- the neural canal becomes the central canal carrying CSF
- alar plates develop into the dorsal horns
- basal plates develop into ventral horns
- the whole spinal cord is surrounded by a thick layer of white matter
Describe the organisation of the nuclei in the brainstem.
- the cranial nerve nuclei within the brainstem that have a motor function tend to lie more medially (because that’s where the basal plates have ended up after the split)
o Motor = Medial
o Sensory = Lateral
o Autonomic = in between
Explain the development of the brainstem.
- the 4th ventricle develops -> makes a mess of the tubular organisation
- the roof plate starts proliferating rapidly causing the dorsal part of the brainstem expands laterally
- as the roof plate expands it pushes the alar plates aside so they are no longer dorsal to the roof plate, this is the developing brainstem
Describe the appearance of the brain at 4 weeks in an embryo.
o only the most anterior bit of the neural tube develops into the brain
- differentiation of the wall of the anterior neural tube occurs to form THREE primary vesicles:
- > prosencephalon = future forebrain
- > mesencephalon = future midbrain
- > rhombencephalon = future hindbrain
o the rest becomes the spinal cord
Describe the appearance of the brain in an embryo at 5 weeks
- enormous expansion of the top part of the developing forebrain -> telencephalon will become the cerebral hemispheres
- less expansion in the lower part of the developing forebrain because that part becomes the diencephalon
- the developing midbrain doesn’t expand very much
- the developing hindbrain divides in two becoming the pons and the medulla
Describe the structure of the brain in a n embryo of 8 weeks of age.
- as development continues you get more and more growth of the wall of the neural tube
- the space within it has become smaller relative to the wall and this space becomes the ventricular system
- late on, you have the first development of the cerebellum -> out-pouching from the back of the pons
Explain the folding of the developing brain.
o there are THREE flexures: cephalic, pontine and cervical
o as you go through development these flexures become exaggerated -> by 8 weeks, the telencephalon has got so big that it’s starting to move back and cover the diencephalon
Explain the development of the cortex
o the brain has a core of white matter with grey matter around the outside -> opposite to the spinal cord
o the grey matter consists of nuclei that have migrated from the inner membrane of the neural tube
- migration takes place by the neuroblasts attaching themselves to radial glial cells -> have their cell bodies anchored in the inner membrane and have a single long process that goes to the outer membrane
- neuroblasts attach themselves to radial glial cells and climb up towards the outer membrane
- a wave of proliferation near the inner membrane occurs followed by a wave of migration towards the other surface -> one layer of the cortex is formed
- another wave of proliferation and another wave of migration forming the 2nd layer of cortex -> continues until you have SIX LAYERS of cells within the cerebral cortex
Back
What are the general causes for the occurence of developmental disorders.
- genetic mutation and environmental factors such as the mother’s lifestyle, diet and teratogens
What is the cause of schizophrenia
- malfunction of neural development early on in develomet
Name a cause of spina bifida
- folic acid deficiency in vivo
What is cranioarchischisis.
- completely open brain and spinal cord
- incompatible with life -> misscarriage, still born or die shortly after birth
What is anenceephaly.
- open brain and lack of skull vault
- as a consequency patients never have a fully developed brain, usually isnt compatible with life (are still born)
What is encephalocele.
- herniation of the meninges (and brain) -> large bump outside of the skull, usually at the back of the head
What is iniencephaly
occipital skull and spine defects with extreme retroflextion of the head
What is spina bifida occulta
- closed asympatomatic NTD in which some vertebrate are not completely closed
What is closed spinal dysraphism
- deficiency of at least two vertebrate arches
- can become covered by lipoma
What is meningocele
- production of the meninges filled with CSF due to a defect in the skull or spine
What is myelomeningocele
- open spinal cord, which can lead to meningeal cysts
Explain the significance of neural stem cells.
- there are still some germinal cells in the subependymal areas and hippocampus of the adult brain, but in very small numbers with none around mid-60s
- after strokes it is sometimes possible for recovery via these stem cells
- research is being done to see if they can be targetted in other neurodegenerative diseases - Huntington’s being one
Define the brainstem.
- the part of the CNS, exclusive of the cerebellum that lies between the cerebrum and the spinal cord
What are the three major divisions of the brainstem from top to bottom?
- midbrain
- pons
- medulla oblongata
State the role of the pineal gland.
- releases melatonin and is important in regulating circadian rhythm -> does so by light via training from vision
What is the role of the superior colliculus.
- important in the coordination of eye and head movements at the same time (think about watching tennis)
What is the role of the inferior colliculus.
- auditory reflexes, if there is a loud bang you tend to look in the direction of the bang immediately
Which cranial nerve emerges from the back of the brainstem?
- trochlear nerve (CN IV) -> out of the back of the pons
State the role of the trochlear nerve
- suppling one of the extrinsic muscles of the eye (superior oblique muscle in particular)
Which sensory pathways are the dorsal corsal columns involved in.
- fine touch
- proprioception (space perception)
What is very clear from the anteroinferior view of the brainstem?
- the pons
Name the 4 functional subtypes of the cranial nerves.
- General Somatic Afferent (GSA)
- General Visceral Afferent (GVA)
- General Somatic Efferent (GSE)
- General Visceral Efferent (GVE)
Describe the function of the special somatic afferent nerve.
- vision, hearing and equilibrium (only the cranial nerves)
State the function of special visceral afferent nerves.
- smell (CN I) and taste
Name the functions of the special visceral efferent nerves.
- muscles involved in chewing, facial expression, swallowing, vocal sounds and turning the head
What is the general rule about the positioning of motor and sensory nerves?
- motor tend to be medial while sensory tend to be lateral
Describe the arrangement of the general somatic efferent nerve.
o GSE are the most medial of all the pathways
- oculomotor = most rostal -> top of the midbrain
- trochlear = immediately below but still in the midbrain
- abducens = in the pons -> nerve move down before emerging from the ponto-medullary junction
- hypoglossal = in the medulla
Describe the anatomy of the special visceral efferent nerves
o SVE lateral to the GSE (2nd)
- trigerminal = in the pons
- facial = in the pons
- ambiguus = in the medulla (involved in swallowing)
- accessory = in the cervical spinal cord
Describe the anatomy of the general visceral efferent nerves.
o GVE are lateral to the SVE (3rd)
- edinger westphal = in the midbrain (parasympathetic imput into the eye)
- salivatory = three pairs of nuclei at the ponto-medullary border
- vagus = in the pons
What is the anatomy of the special somatic afferent nerve.
o most lateral (6th)
- vestibulocochlear = nucleus mainly resides in the pons but also partly in the medulla
What is the arrangement of the general somatic afferent nerves?
o lateral to the GVA (5th)
- there are THREE trigerminal nuclei, one spans across from the midbrain to the pons, another is completely in the pons while the last starts in the pons and goes all the way down the cervical spinal cord
Describe the arrangement of the general visceral afferent nerve.
o most medial of the sensory nuclei but still lateral to all motor (4th)
- solitarius = 90% in the medulla with a fraction in the pons
Describe the appearance of the midbrain.
- has a typical MICKEY MOUSE appearance
- you can see the cerebral aqueduct then you’re in the midbrain
- cerebral peduncle will vary in appearance
- the inferior colliculus which is low down in the midbrain
- MOST OBVIOUS SIGN IS THE SUBSTANTIA NIGRA -> are dopaminergic neurones which normally produce neuromelanin, a pigment that gives its BLACK colour -> as you get old it gets blacker and blacker
NOTE: In Parkinson’s disease you lose these dopaminergic neurones so a pale substantia nigra could be a sign of Parkinson’s disease
What is the anatomy of the pons?
o the pons is in the region of the 4th Ventricle - just underneath the cerebellum
o MOST PBVIOUS FEATURE ARE THE TRANSVERSE FIBRES
o cerebral peduncles hold onto the cerebrum onto the back of the brainstem
- the main peduncle is the middle cerebellar peduncle
Describe the anatomy of the open/upper medulla.
- the medulla changes a lot as you go down the brainstem
- at the top you still have the 4th ventricle but the rest of the shape is very different to the pons
- MAIN FEATURE = PYRAMIDS start to be seen
- a bit of a bulge in the side of the medulla called the inferior olivary nucleus - this is connected to the cerebellum and is involved in fine tuning motor movements
- inferior olivary nucleus can be seen
Wha is the anatomy of the lower medulla?
o at the junction with the spinal cord the cross-section is very round
o dorsal columns can be seen here (touch and proprioception)
- the smaller of the columns is the gracilis - sensory information from the lower limb
- more laterally you have the cuneatus - sensory information from the upper limb
o central canal can be seen in the cross-section of the lower medulla
o crossing over of the fibres at the pyramidal decussation in the lower medulla
State the signs and symptoms of Lateral Medullary Syndrome.
- vertigo
- ipsilateral Cerebellar Ataxia - problem with gait on the same side of the body as the lesion (broad-based gate with a tendency to shuffle)
- ipsilateral loss of pain/thermal sense (face)
- Horner’s Syndrome - loss of sympathetic innervation to the head and neck -> ptosis, lack of sweating around the eye, hoarseness of voice and difficulty swallowing
- contralateral loss of pain/thermal sense in the trunk and limbs
What is the cause of lateral medullary syndrome?
- caused by thrombosis of the vertebral artery or the posterior inferior cerebellar artery
Using this image match the areas to the consequences of lateral medullary syndrome.
- PICA supplies the shaded section of the medulla
- disturbing the vestibular nucleus = vertigo
- disturbing the inferior cerebellar peduncle = the balance problem
- sympathetic tract = Horner’s Syndrome
- spinothalamic tract = pain and sensory information coming from the body
- damage is catastrophic because everything is packed close together in the medulla
What are the demands of the brain?
- 2% of his body weight (around 1.3 kg)
- 10-20% of CO
- 20% of body oxygen consumption
- 66% of liver glucose
- brain is very vunerable if blood supply becomes impaired
What are the two blood supplies to the brain?
- internal carotid arteries (front)
- vertebral arteries (back)
Name the structure that the ICA and VA give rise to.
- circle of Willis
- cerebral arteries come off the circle
Where do the external carotid arteries supply?
- the face
What arteries supply the cerebral hemispheres?
- internal carotid
Describe the pathway of the vertebral arteries which branch of the subclavian arteries.
- travel through the tranverse foramina in the cervical vertebrate and the foramen magnum and onto the brain
Name the major vessels in the venous drainage of the brain.
- cerebral veins
- venous sinuses
- dura mater
- internal jugular veins
Describe the system of the dural venous sinuses
- running along the top is the superior sagittal sinus, inbetween the two folds of dura, at this point the CSF drains back into the venous system
- along the bottom of the dural fold is the inferior sagittal sinus
- these sinuses run backwards to form a big space filled with blood called the CONFLUENCE OF THE SINUSES -> a bleed at the confluence of sinuses can be terrible
What is the medical term for a stroke?
- cerebrovascular accident (CVA)
Define Stroke.
- rapidly developing focal disturbance of brain function of presumed vascular origin lasting more than 24 hours
What percentage of strokes are due to infarction?
- 85%, the other 15% is due to haemorrhage
Define Transient Ischaemic Attack (TIA).
- rapidly developing focal disturbance of brain function of presumed vascular origin that resolves completely within 24 hours
Why are TIA clinically so important?
- a massive risk factor for a stroke -> may have been a small bit of atherosclerotic debris that blocks more distally and resolves itself
State 2 causes of occlusions.
- thrombosis -> formation of a blood clot
- embolism -> plugging of small vessel by material carried from larger vessel
How many people die of strokes each year in the UK?
- 100,000, making it the 3rd most common cause of death
What perecentage of survivors have some kind of damage?
- 70% show an obvious neurological defect
- 50% are permenently disabled
Name 5 key risk factors to having a stroke.
- age
- hypertension
- cardiac disease
- smoking
- diabetes mellitus
Describe the path of the middle cerebral artery.
- extends laterally and emerges through the lateral fissure between the frontal and temporal lobes
State the area which is supplied by the middle cerebral artery.
- it supplies the front 2/3 of the lateral part of the hemisphere
Which section of the brain is supplied by the posterior cerebral artery?
- posterior cerebral artery supplies the medial and lateral parts of the posterior part of the hemisphere
What artery supplies the medial part of each hemisphere?
- the anterior cerebral artery
State the symptoms specific to a stroke caused by disturbance to the anterior cerebral artery.
- paralysis of the contralateral LEG more so than the arm or face -> due to motor homunculus part of the motor cortex that controls the leg is more medial than the part controlling the arm
- disturbance of intellect, executive function and judgement (abulia - absence of willpower)
- loss of appropriate social behaviour
State the symptoms specific to a stroke caused by disturbance to the middle cerebral artery.
- CLASSIC STROKE
- contralateral hemiplegia - more the contralateral ARM than leg -> the lesion is more lateral -> closer to the motor cortex controlling the arms than legs
- contralateral hemisensory deficits
- hemianopia (loss of half the visual field)
- aphasia (if a left sided lesion) - can’t speak -> the language centres are more on the left side of the brain
What are the areas of the brain involved in speech?
- Broca’s Area
Name the symptoms specific to a stroke caused by disturbance to the posterior cerebral artery.
o this leads to visual defects -> supplies the occipital lobe where the primary visual cortex is
- omonymous hemianopia
- visual agnosia (loss ability to recognise things)
Back
What are lacunes?
- a lacune is a small cavity, that appear in deep structures as a result of small vessel occlusion, the exact deficit is dependent on anatomical location
- often caused by strokes
Name a cause of lacunar infarcts.
- hypertension
Name the 4 types of haemorrhagic strokes.
- extradural
- subdural
- subarachnoid
- intracerebral
State the cause and consequence of extradural haemorrhagic strokes.
- trauma
- immediate effects - high pressure arterial bleed -> massive increase in intracranial pressure -> herniation -> will be terminal if surgical intervention to relieve pressure is not carried out
- it treated quickly it has good prognosis
State the cause and consequence of a subdural haemorrhagic stroke.
- trauma
- delayed effects due to lower pressure venous bleed -> blood accumulates in the subdural space -> still an emergency -> good outcome if treated
- not uncommon for them to have been initial unconscious and then to have recovered
State the cause of subarahnoid haemorrhagic stroke.
- usually a ruptured aneurysm
State the cause of intracerebral haemorrhagic stroke.
- spontaneous hypertensive rupture of small vessels
What is the difference between dura in the skull and in the vertebral column?
- vertebral column has a SINGLE LAYER of dura with fat between the bone and the dura
- the skull has TWO LAYERS of dura that are mostly stuck together
What are the two layers of dura in the skull?
- periosteal
- meningeal
Describe an extradural haematoma.
- high pressure arterial supply to the brain leads to the splitting of some of the arteries that are running in the meninges themselves (between the dura and the skull), causing compression of the skull underneath
- the periosteal dura is stuck to the skull so it is only a potential space that is there, which can be filled by blood in an extradural haemorrhage
- usually always due to a blow to the side of the head
Describe a subdural haematoma.
- are slower to cause issues than an extradural haematoma
- is caused by the rupture of VEINS in the skull - so is at much lower pressure
- because of the slow onset of symptoms, patients may initially think that they are ok and then experience symptoms a few hours later
What is the fold of dura that extends between the medial surfaces of the two hemispheres called?
- falx cerebri
What does the peeling apart of the two layers of dura at the top of the falx cerebri form and what is found in this space?
- superior sagittal sinus
- within the gap arachnoid granules are found
How is the CSF filtered?
- it leaks through holes in the arachnoid membrane and enters the superior sagittao sinus
Which vertebrate is the most to likely herniate?
- L5 disk -> change in angle between lumbar vertebra and sacral -> has the most pressure going through it
In terms of meningeal layers, what are the differences between the brain and the spinal cord?
- no epidural space in the brain unless a pathological issue is present but there is in the spinal cord
- two layers/folds of dura around to the brain but only one around the spinal cord
- if there isn’t a space then there is some sort of pathology present -> haemorrhage being one
From the outside travelling inwards, name the meningeal layers and the space linked to them around the spinal cord.
- epidural space
- dura mater
- arachnoid mater
- subarachnoid space
- pia mater
State some clincial relevances of the epidural space.
- can be used to insert anaesthetic or painkillers -> sometimes done in childbirth
- epidural nerve block for pain relief or to carry out surgery
State the clincial relevance of the subarachnoid space.
- sampling of CSF
- insertion of anaesthtics or painkillers-> if there is a good idea of how long a surgery will take it is used instead of a general anaesthetic -> especially in the elderly or those with co-morbidites
- spinal nerve block for pain relief or to make surgery possible
Define dermatomes.
- an area of skin that is supplied by a pair of neurones
Define myotome
muscles that are supplied by a pair of neurones
Which spinal nerve supplies the dermatome that the umbilicus lies in?
- T10
At what point does a nerve become a mixed spinal nerve?
- once the sensory and motor nerve have joined laterally from the roots
Describe the cross section the spinal cord, including some key landmarks.
What is the general rule about sensory neurone crossing in the spinal cord.
- sensory neurones usually cross over when it synapses -> if the neurone synapses when entering spinal cord it will immediatelycross etc
When do discriminative touch and proprioception sensory fibres cross over?
- sensory fibres enter the dorsal horn and travel in the dorsal columns without synapsing in the posterior horn so don’t cross until the medulla
When do pain and temperatue sensory fibres cross over?
- sensory fibres enter the dorsal horn, then may travel up or down 1-2 segments in the Lissauer tract, and synapse in the nucleus proprius before crossing the midline in the anterior commissure and travelling in the spinothalamic tract
At what point do motor neurones cross over?
- all motor neurones cross over deep in the medulla, therefore they always emerge on the ‘correct’ side
Name the major tracts the spinal cord in a clockwise direction form back to front while also stating their function.
o corticospinal tracts = voluntary movement pathway
- lateral = limbs
- anterior = trunk (proximal muscles)
o spinothalamic tract = pain and temperature from contralateral side of body
o dorsal columns = sensory info for fine (discriminative) touch
- fasciculus gracillis – lower limbs
- fasciculus cuneatus – upper limbs
What is the path of the lateral corticospinal tract?
- a neurone travels from the fine motor cortex to the medulla where is synapses and therefore crosses over before a spinal nerve which synapses onto a lower motor neurone before becoming a periphary nerve with other spinal nerves and travelling to an effector/muscle
Name some factors that affect the severity of spinal lesions.
- loss of neural tissue - small if due to trauma but extensive if due to metastases or degenerative disease
- vertical level
- transverse plane
What is the link between the height of a lesion and the level of disability?
- the higher the lesion, the greater the disability
- REMEMBER C3,4,5 keep the diaphragm alive -> segmets which the phrenic nerve emerges from
Why is the brains glucose supply so surplus?
· the brain can’t synthesise or utilise any other source of energy, estimated that the brain use 50-60% of the bodies glucose
· ketones can be metabolised, for a short period of time, if there is a shortage of glucose but glucose is the main nutrient
Describe the stages of lateral corticospinal tract injury including recovery
· Stage 1 - spinal shock: loss of reflex activity below the lesion, lasting for days or weeks = flaccid paralysis
· Stage 2 - return of reflexes (happens over weeks/months): hyperreflexia and/or spasticity = rigid paralysis
What percentage decrease in blood flow to the brain is required before its function becomes significantly impaired?
- 50%
State the consequence of a 4 second interruption of cerebral blood flow.
- unconsciousness
- after a few minutes irreversible damage starts to occur
Describe the symptoms of hypoglycaemia caused by the loss of brain function.
- individual appears disoriented
- slurred speech
- impaired motor function
o similar to be being drunk
What is the blood glucose conc. that if values fall below becomes catastrophic?
- below 2 mM (normally between 4-6mM) it can result in unconsciousness, coma and DEATH
How is cerebral blood flow maintained?
- via autoregulation by stretch-sensitive cerebral vascular smooth muscle which can contact and relax to maintain cerebral blood flow when arterial blood flow is between 60-160mmHg
What happens if the arterial blood flow rises above 160mmHg?
- increased flow can lead to swelling of brain tissue which is not accommodated by the “closed” cranium, therefore intracranial pressure increases -> becomes dangerous
What two factors contribute to local regulation of cerebral blood flow?
- neural
- chemical
Describe the pattern of vascularisation in the CNS tissues.
- arteries enter the CNS tissue from branches of the surface pial vessels, branches penetrate into the brain parenchyma branching to form capillaries which drain into venules and veins which drain into surface pial veins
- no neurone is ever more than 100µm from a capillary
What 4 neural factors alter local cerebral blood flow?
- sympathetic nerve stimulation -> vasoconstriction - only happens when the arterial blood pressure is HIGH
- parasympathetic (facial nerve) stimulation -> facial nerve fibres are innervated by parasympathetic fibres -> causes a slight vasodilation
- central cortical neurones -> neuronal neurotransmitter (catecholamines) release -> vasoconstriction)
- dopaminergic neurones -> produce vasoconstriction -> important in regulating local blood flow to areas of the brain that are more active
Define pericytes.
- cells that wrap around capillaries which have diverse activities e.g. immune function, transport properties, contractile
- effectively a type of brain macrophage
Explain how dopaminergic neurones control local cerebral blood flow.
- when dopaminergic neurones are active, they can cause the contraction of pericytes to decrease the blood flow to a particular area thus diverting blood to other, more active areas of the brain
- dopamine may also cause contraction of pericytes via aminergic and serotoninergic receptors
- IMPORTANT FOR DIVERTING BLOOD TO ACTIVE AREAS OF THE BRAIN
What chemical factors can alter local cerebral blood flow?
- CO2 (indirect) -> vasodilator
- pH -> vasodilator
- nitric oxide -> vasodilator
- K+ -> vasodilator
- adenosine -> vasodilator
- anoxia -> vasodilator
- other (e.g. kinins, prostaglandins, histamine, endothelins)
Explain how CO2 can cause cerebral artery flow to increase.
- H+ ion cannot cros the BBB to influcence smooth muscle cells
- CO2 from the blood or from local metabolic activity gets converted to H+ by carbonic anhydrase in surrounding neural tissue and in the smooth muscle cells -> elevated H+ means decreased pH -> relaxation of the contractile smooth muscle cells and increased blood flow
Where is the CSF formed?
- choroid plexus -> are present in the lateral ventricle, 4th ventricle etc
Name an adaptation that makes the choroid plexus good for CSF formation.
- the capillaries are leaky but, are surrounded by ependymal cells with tight junctions -> can freely lsecrete molecules into the ventricle to make CSF
Describe the flow route of CSF.
lateral ventricles -> 3rd ventricle (via interventricular foramina) -> cerebral aqueduct -> 4th ventricle -> subarachnoid space (via medial and lateral apertures) -> lateral ventricles
State the volume of CSF as well as the amount produced formed everyday.
- volume of CSF = 80 - 150 mL
- volume of CSF formed per day = 450 mL/day
What is the function of the CSF?
- protection (chemical and physical)
- nutrition of neurones
- transport of molecules
What are the functions of the Blood-Brain-Barrier?
- protects the brain tissue from toxins and circulating transmitters like catecholamines
- it also protects the brain from wide variations in ion concentrations
Compare plasma to CSF.
o very similar composition
- amino acids are much lower in CSF, Ca2+ and Na+ are also lower
- CSF has very little protein where plasma has a lot
What is the clinical relevance of there being very little protein in CSF?
- if there is protein in the CSF it is a marker for brain infection, injury or other damage
What is Brown-Sequard Syndrom?
- a rare neurological condition characterized by a lesion in the spinal cord which results in weakness or paralysis (hemiparaplegia) on one side of the body and a loss of sensation (hemianesthesia) on the opposite side
What changes occur in a vessel of the CNS parenchyma as it travels away from the pial?
- the junctions become tighter and therefore the vessel become less and less permeable
What classes of molecules can relatively easily cross the BBB?
- lipophilic molecules (alcohol and anaesthetics)
- hydrophobic
How do hydrophilic substances cross throught the BBB and into the brain and CSF?
o only certain hydrophilic substances are allowed through the BBB by means of specific transport mechanisms including:
- water via aquaporin channels
- glucose via GLUT1 proteins
- amino acids via 3 different transporters
- electrolytes via specific transporter systems
What are the general roles of circumventricular organs (CVOs)?
- sampling plasma for toxins -> will induce vomiting
- sensing electrolytes
- regulating water intake
Name some circumventricular organs (CVOs)
- median eminence region of the hypothalamus
- subfornical organ (SFO)
- organum vasculosum of the lamina terminalis (OVLT)
What is special about circumventricular organs?
- even though they are in the brain they lie outside of the BBB and actually have fenestrated capillaries
- molecules can readily pass from the blood to the CSF/ ECF -> vital for their relative functions
- ventricular ependymal lining close to these areas can be much tighter than in other areas, limiting the exchange between them and the CSF
Name some pathological states that cause the breakdown of the BBB.
- inflammation
- infection
- trauma
- stroke
How does the BBB affect the treatment for Parkinson’s Disease?
o a key therapy in Parkinson’s disease is pharmacologically raising the levels of dopamine in the brain, however dopamine cannot cross the BBB
o L-DOPA can cross the BBB via an amino acid transporter, and is converted to dopamine in the brain by DOPA decarboxylase -> is a pharmacology way of increasing dopamine in the brain
- however lots of L-DOPA gets converted before it reaches the brain -> L-DOPA is co-administration with a DOPA decarboxylase inhibitor (carbidopa) -> carbidopa cannot cross the BBB, so does not affect conversion of L-DOPA in the brain
What is the problem of using L-DOPA as a treatment for Parkinson’s Disease?
- lots of L-DOPA is converted to dopamine outside of the brain by DOPA decarboxylase, reducing the conc. of L-DOPA which can cross the brain
- can’t raise does or adverse effects of dopamine appear
How are the problems with L-DOPA overcome for Parkinson’s treatment?
- co-administrating a DOPA carboxylase inhibitor (carbidopa)
- carbidopa cannot cross the BBB so enzymes instead the BBB aren’t inhibited
What is a modality?
- a type of stimulus -> hot, cold, touch, etc
- each modality has a specialised receptors which transmit information through specfic anatomical pathways to the brain
What is registered by mechanoreceptors?
- touch, pressure, vibration
- proprioception -> joint position, muscle length, muscle tension
What receptors sense temperature?
- thermoreceptors
What is the receptor for pain?
- noiceptors
What sensory information is carried by A-alpha fibres?
- proprioception of skeletal muscles
What sensory information is carried by A-beta fibres?
- mechanoreception of skin
What sensory information is carried by A-gamma fibres?
- pain
- temperature
What sensory information is carried by C fibres?
- temperature
- pain
- itch
Define Sensory Receptor.
- transducers that convert energy from the environment into neuronal action potentials
Define Absolute Threshold.
- the level of stimulus that produces a positive response of detection 50% of the time
Describe thermoreceptors, including their activation.
- free nerve endings with high thermal sensitivity
- changes in temperature activates a family of transient receptor potential ion channels
What do Meissner’s corpuscles detect?
- fine discriminative touch
What do Merkel cells detect?
- light touch and superficial pressure
What do Pacinian corpuscles detect?
- deep pressure, vibrations and tickling
What do Ruffini endings detect?
- continuous pressure or touch and strech
How sensitive are mechanoreceptors?
- very -> have a very low threshold
What are tonic receptors?
o detect continuous stimulus strength -> transmit impulses to the brain as long the stimulus is present -> keeps the brain constantly informed of the status of the body
o slowly adapting
- eg. merkel cells-> slowly adapt allowing for superficial pressure and fine touch to be perceived
What are phasic receptors?
o detect a change in stimulus strength -> transmit an impulse at the start and the end of the stimulus
o slowly adapting
- e.g. pacinian receptor -> sudden pressure excites receptor causing a signal, transmits a signal again when pressure is released
Define Receptive Field.
- a region on the skin which causes activation of a single sensory neuron when activated
What is the significance of the receptive fields, when talking about sensitivity?
- finger tips, lips, tongue have high density of innervation with very small receptive fields = more sensitive
- the back has less densely packed innervation with larger receptive fields = less sensitive
What is two point discrimination and how does it tie in with receptive fields?
o minimum distance at which two points are perceived as seperate
- is related to the size of receptive fields -> points can be closer on the hand than the back
What is tranduction?
- sensory receptors generate a receptor potential, a change in their membrane potential, in response to approriate stimulation
Where does the cuneate nucleus recieve input from?
- C1-T6 -> via the cuneate tract
What imputs into the gracile nuclues?
- T7-S4 -> via the gracile tract
In terms of sensory input, what is area 3b involved in?
- tactile discrimination
In terms of sensory input, what is area 1 involved in?
- analysis of texture
In terms of sensory input, what is area 2 involved in?
- stereognosis -> ability to percieve the 3D shape of an object by touch
- has input from muscles and joints and reciprocal connections with the motor cortex -> may inform the motor cortex of sensory consequences of moving
What inputs into the primary somatosensory cortex?
- input from a single type of receptor, and from a specfic location
What inputs into the secondary somatosensory cortex?
- input from the thalamus and primary somatosensory cortex
- many neurons in the SII have bilateral receptive fields -> stimuli in corresponding regions on both sides of the body will evoke a response
How is the secondary somatosensory cortex able to form a whole body perceptual experience?
- inputs from the contralateral body surface arise directly due to decussation (crossing over) of the medial lemniscus
- inputs from the ipsilateral body surface enter secondary somatosensory cortex from the contralateral side via the corpus callosum
- by integrating information from both sides the SII is the first stage in froming whole body perceptual experiences
What are the roles of the secondary somatosensory cortex?
- enable tactile discrimination learned using one hand to be easily performed with the other -> due to its input into the limbic cortex
- important in controlling movement in the light of somatosensory input via its connections with the motor cortex
Explain how we are not aware of the sensations caused by wearing clothes.
- the somatosensory cortex has reciprocal connections with all of the subcortical structures which relay sensory input to it
- the descending pathway is made by the corticospinal (pyramidal) tract either directly or via its connections witht he brainstem reticular nuclei -> these back projections have a somatotopic mapping precisely in register with the ascending dorsal column-medial lemniscal system -> this is the vehicle which somatosensory input is filtered as an attention mechanism
What is the difference between nocieptive and pathological pain?
- nociceptive (acute) has a protective role
- pathological (clinical) is associated with disease and nervous system dysfunction
What is the name given to the area of skin innervated by a dorsal root?
- dermatome
What is conveyed by the anterolateral pathways?
- temperature
- pain
- crude touch sensation
Name 4 characteristics of nociceptors.
- polymodal -> different types of nociceptor respond to different types of stimuli
- free nerve endings -> in terms of structure they are much simpler than mechanoreceptors, usually just free axonal endings of sensory neurones
- high threshold - higher activation threshold than touch receptors
- slow Adapting -> good because if there is a potentially harmful stimulus then you want to be constantly reminded of it so you do something about it
What two sensroy fibres carry nociceptive information?
- A-delta
- C neurone
Describe A-delta fibres.
- large
- fast adapting
- produces pain fast -> alerts you to the potential of some harmful scenario
- fast conducting -> still no where near as fast as touch neurones
Describe C neurones.
- smaller than A-delta neurones
- produces a dull, aching pain -> the role of C neurone mediated nociception is to remind you of the injury so that you guard this part of the body
- slow conducting -> unmyelinated -> ties in with its role/provides a constant reminder
Where does input pass through as it goes from the peripheral to central nervous system?
o the dorsal root
- dorsal root ganglion (body)
- trigeminal ganglia (face)
Where is the dorsal horn situated and how is it organised?
- part of the spinal cord
- organised into rexed laminae (I-VII)
Where exactly does innocuous mechanical stimuli input into the dorsal horn?
- A-beta fibres terminate in lamina III-VI -> deep in the dorsal root
Where exactly does pain and temperature stimuli input into the dorsal horn?
- A-delta and C-fibers terminate in lamina I-II -> supericial
What is the main excitatory neurotransmitter in the dorsal horn?
- glutamate
How do interneurons connect?
- between different laminae and between adjacent peripheral inputs
What is lateral inhibition used for?
- to detect the difference between adjacent inputs
How can rubbing an injured area provide pain relief?
- rubbing the skin stimulates the A-beta fibres -> inhibits stimulated pain fibres by interneuron inhibition
What travels in the dorsal column system?
o innocuous mechanical stimuli
- fine discriminative touch
- vibration
How do A-beta fibres enter the dorsal column pathways?
- through the dorsal horn
Where are the gracile and cuneate nuclei postioned?
- in the medulla
Where do 2nd order neurones of the dorsal column cross the in the medulla?
- caudal medulla -> forms the contralateral medial lemniscus tract -> travels and terminates in the ventral posterior lateral nucleus of the thalamus
Where do 3rd order neurones of the dorsal column project to?
- somatosensory cortex -> size of somatotopic areas in proportional to density of sensory receptors in that body region - somatosensory humunculus
Where do 1st and 2nd order neurons of the spinothalamic tract terminate?
- 1st = dorsal horn
- 2nd = decussate immediately in the spinal cord and form the spinothalamic tract and terminate in the ventral posterior lateral nucleus of the thalamus
What is the spinoreticular tract?
- the pathway which links pain to the limbic cortex and tehrefore emotion
What is the main cause of an anterior spinal cord lesion?
- blocked anterior spinal artery causes ischaemic damage to the anterior part of the spinal cord
What are the symptoms of an anterior spinal cord lesion?
- bilateral loss of pain and temperature below the lesion -> spinothalamic tract is damaged
- retained light touch and vibration sensation -> dorsal column is fine
What is Electrical Perceptual Thresholds (EPT)?
- a technique in which an electronic pulse is passed to the skin
- used to determine the type and location of a spinal cord injury
Define pain.
- an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
State the types of pain.
- nociceptive -> tissue damage, typical ACUTE (e.g. cut skin)
- muscle -> lactic acidosis, ischaemia (e.g. strecthing, fibromyalgia)
- somatic -> well localised (e.g. inflammation, infection)
- visceral -> deep, poorly localised pain (e.g. stomach, colon, IBS)
- referred -> from an internal organ/structure (angina, appendicitis)
- neuropathic -> dysfunctional nervous system
How long does pain last for before it would be counted as chronic?
- 6 months
Define neuropathic pain.
- pain cuased by a lesion or disease of the somatosensory nervous system
What does neurpathic pain feel like?
- sharp, burning, electric shock like
How does neuropathic pain respond to opiates?
- poorly
- anti-depressants are commonly used instead -> particularly TCAs
What is sciatica?
- pain caused in the sciatic nerve due to spinal nerves becoming compressed in the intervertebral foramen
Name 5 examples of neurpoathic pain.
- sciatica
- diabetic neuropathy
- post-herpetic neuralgia
- post-surgical pain
- HIV-induced neuropathy
- chemotherapy indcued neuropathy
- complex regional pain syndrome
Define Allodynia.
- pain due to to a stimulus that does not normal provoke pain
Define Hyperalgesia.
- increased pain from a stimulus that normally provokes pain
Define Sensitisation.
- increased responsiveness of nociceptive neurons to their normal input
- a research driven phrase
Define Hypoalgesia.
- a diminised pain in response to a normally painful stimulus
Define Paraesthesia.
- abnormal sensation, whetehr spontaneous or evoked
How is neuropathic pain diagnosed/assessed?
- questionnaires
- simply examination techniques -> cold/freezing pain, brus, pin prick
What is mechanism behind a repeated painful stimulus becoming more painful when it is repeated?
- intiated by NMDA receptor activation
- Ca2+ mediated synpatic plasticaity in dorsal horn neurons
- increased synaptic strength
- reduced inhibtory influences on dorsal neurons
- persistant activation of NMDA receptors can result in the development of chronic pain
What is the role of monoamines?
- inhibit spinal cord excitability
What is the descending control of nociception with the PAG-RVM axis and locus cereleus?
- PAG-RVM = serotonin
- locus cereleus = noradrenaline
How might endogenous opiods affect peoples pain thresholds?
- endogenous opiods are contained within the PAG and RVM
o they enhance the inhibition from the PAG-NVM axis -> reduces the pain transmission in the dorsal horn by inhibitng glutamate release -> activates spinothalamic neurons and therefore inhibition of pain
- this mechanism works when placebos are given
Name some pain relief drugs that work in the descending control systems?
- opiods
- anti-depressants -> TCA, SNRI, SSRI
What is the mechanism of Serotonin and Norepinephrine Re-uptake Inhibitors (SNRIs) mechanism in descending noradrenaline inhibition?
- binds to the pre-synaptic (sometime post) terminal in the dorsal horn and therefore increases the amount of noradrenaline in the cleft
- noradrenaline binds to alpha 2 receptors -> inhibitory signalling in that neurone
What are the 3 neuropathic pain ‘clusters’?
- sensory loss
- thermal hyperalgesia
- mechanical hyperalgesia
What is Functional Segregation?
- motor systems organised in a number of different areas that controls different aspects of movement
What is meant by Hierarchical Organisation?
- high order areas are involved in more complex tasks -> programme and decide on movements, coordinate muscle activity
- lower level of the hierarchy performs lower level tasks -> execution of movement
Describe the Motor System Hierarchy.
o Level 1 = spinal cord -> mainly involved in reflex movements
o Level 2 = Brainstem -> is the centre of integration of different inputs coming from the vestibular system, the vision system and the auditory system
o Level 3 = Motor Cortex (consists of the: primary motor cortex, premotor cortex and supplementary motor area) -> is where the movements are programmed and where the voluntary movements are initiated
- Level 4 = Association Cortex (contains the parietal and frontal cortex) -> not strictly part of the motor pathway, but it influences the planning and execution of movements
What is the role of the basal ganglia and cerebellum in movement?
- basal ganglia and cerebellum fine tune the corse instruction from the primary motor cortex before it reaches the spinal cord
What is the anatomical pathway which from wanting to move to movement?
Where is the primary motor cortex located?
- precentral gyrus, anterior to the central sulcus
What is the function of the primary motor cortex?
- controlled fine, discrete, precise voluntary movement
- provides descending signals to execute movement
What are the 3 parts of the motor cortex?
- Primary Motor Cortex or M1 - Broadmann’s Area 4
- Premotor Cortex - Broadmann’s Area 6
- Supplementary Motor Area - Broadmann’s Area 6
How is the primary motor cortex arranged?
- somatotopic organisation
Where is the vestibulocerebellum?
- deep, inner section of the cerebellum
Where is the spinocerebellum?
- medial section of the cerebellum
Where is the cerebrocerebellum?
- lateral area of the cerebellum
What is the arrangement of alpha motor neurones in the spinal cord?
- extensors = more anterior part of the ventral horn
- flexors = more posterior part of the ventral horn
- proximal = more central
- distal = more lateral
What are the 4 aspects of the active process of hair bundles in the inner ear?
- amplification
- frequency tuning
- compressive non-linearity
- spontaneous otoacoustic emission
What is the anatomy of the eye?
Label the diagram.
What are the 5 layers of the cornea?
- Epithelium -> regenrates very quickly
- Bowman’s Membrane
- Stroma -> thickest layer of the cornea -> contributes towards transparency -> corneal nerve endings provides sensation and nutrients for healthy tissue as no blood vessels are in normal cornea
- Descemet’s Membrane
- Endothelium -> pumps fluid out of corneal and prevents corneal oedema -> no regeneration power and the density decreases with age -> endothelial cell dysfunction may result in corneal oedemaand corneal cloudiness
What is refraction?
- based on the idea that light is passing through one medium into another -> as light goes from one medium to another, the velocity changes
- ratio of two speeds can be compared:
Describe how a stroke can lead to macular sparing homonymous hemianopia.
- leads to Contralateral Homonymous Hemianopia with Macula Sparing -> area representing the Macula receives dual blood supply from Posterior Cerebral Arteries from both sides
Describe the Papez circuit.
- main output pathway of the hippocampus is the fornix, which comes out of the inferior horn of the lateral ventricle (the hippocampus sits in the ventricle floor) -> fibres go up, forward and down into the mammillary bodies of the hypothalamus -> a connection to the anterior nucleus of the thalamus via the mamillo-thalamic tract -> projections from the thalamus to the cingulate cortex (just above the corpus callosum) -> to complete the circuit, there are fibres running from the cingulate cortex to the hippocampus (via the cingulum bundle
Describe a graph showing awareness against vigilance.
What is the default-mode network?
- a pathway which is more active at rest/inbetween tasks
Define a coma.
Define vegetative state.
Define minimally active state.
What are the paramater/scoring systems for the glasgow coma scale?
What is shown on this scan?
- extradural haemorrhage
What is shown on this scan?
- subdural haemorrhage
What is shown on this scan?
- diffuse axonal injury
What is shown on this scan?
- posterior fossa lesions -> compresses the brain stem
What is shown on this scan?
- bilateral medial thalamic infarcts
Label this diagram.
