Lec 1 How the Brain is Different Flashcards
0
Q
Is there lymphoid drainage in the brain?
A
Nope! has CSF system instead
1
Q
What is glial cell response to injury?
A
form scars not fibroblasts
2
Q
How many neurons in the brain?
A
> 100 billion
3
Q
What is embryo origin of neurons?
A
ectoderm
4
Q
Can neurons be replaced?
A
No – after earliest days of infancy likely cannot be replaced
5
Q
What is the perikaryon?
A
cell body of a neuron
6
Q
What are the 3 main parts of the neuron?
A
- cell body (perikaryon)
- axon
- dendrites
7
Q
What is the receptive part of the neuron? The part that sends the output?
A
- dendrites receive input
- axons send output to synapse
8
Q
Are there more glial cells or neurons in the brain?
A
glial cells out-number neurons by 20x
9
Q
What are the 4 types of glial cells?
A
- astrocytes
- oligodendroglia
- ependymal cells
- microglia
10
Q
What type of glial cell makes of 20-50% of human brain volume?
A
astrocytes
11
Q
What is embryonic origin of astrocytes?
A
ectoderm
12
Q
What is function of astrocytes?
A
- physical support (structural framework)
- part of blood-brain barrier
- supply glutamate to neurons
- metabolic support (provide neurons with nutrients)
- maintain ion balance in extracellular space (take up K that active neurons are releasing)
- glycogen fuel reserve buffer (capable of glycogenesis, store and release glycogen for neurons to use)
- repair nervous system
13
Q
What 4 structures in the CNS/PNS come from the neuroectoderm?
A
- CNS neurons
- ependymal cells (inner lining of ventricles)
- oligodendroglia
- astrocytes
14
Q
What 2 structures in CNS/PNS come from the neural crest?
A
- PNS neurons
- Schwann cells
15
Q
What structure in the CNS/PNS comes from the mesoderm?
A
microglia (M for Microglia, also Macrophages!)
16
Q
Which parts of the neuron can be stained via the nissl substance? why?
A
- cell bodies and dendrites can because nissl substance stains RER
- RER is not present in the axon so axon does not stain
17
Q
What marker is used to identify astrocytes histologically?
A
GFAP
18
Q
What is the function of oligodendroglia?
A
- myelinate axons of CNS neurons
- each cell myelinates ~30 axons
19
Q
What is the main type of glial cells in white matter?
A
oligodendroglia
20
Q
What is the embryological origin of oligodendroglia?
A
ectoderm
21
Q
Which type of glial cells gives fried egg appearance on H&E?
A
oligodendroglia
22
Q
What is histo appearance of ependymal cells?
A
epithelial like, ciliated, simple cuboidal
23
Q
What is histo appearance of ependymal cells?
A
epethelial like, ciliated, simple cuboidal
24
What is function of ependymal cells?
- line CSF-filled ventricles in brain and central canal of spinal cord
- cilia on their apical surface help circulate CSF around
- microvilli on their surface absorb CSF
25
WHat is the choroid plexus?
- system of modified ependymal cells and capillaries that produce CSF
26
What is function of microglia?
- macrophage of brain and spinal cord (CNS)
- respond to parenchymal tissue damage / pathogens / toxins by differentiating into large phagocytotic cells and proliferating
- phagocytoses neurons that undergo programmed death during development
- no known function in resting state
- monitor CNS environment and restore homeostasis after CNS injury
27
What is function of microglia
resident macrophage of brain and spinal cord
28
What is embryo origin of microglia?
mesoderm
29
What is histo shape of microglia in non-activated vs activated state?
non-activated: small irregular nuclei, little cytoplasm
| active: large rod-shaped nuclei, bigger cyto
30
What is neuronophagia?
microglia encircle degenerating neurons
31
What happens to microglia with age?
-- get progressively more activation in absence of stimulation
-- may contribute to neurodegeneration that occurs in Alzheimer's, Parkinson's, HIV encephalopathy
32
What happens to microglia with age?
-- get progressively more activation in absence of stimulation
-- may contribute to neurodegeneration that occurs in alzheimers, parkinsons, HIV encephalopathy
33
What are the 3 ways the brain is sequestered by glial cells from rest of body?
- blood-brain barrier
- spatial buffering (maintenance of ion balance in extracellular fluid
- active supervision of neuronal microenvironment
34
What is the blood brain barrier?
- controlled transcapillary transport
| - prevents passage large molec from blood into interstitial fluid of CNS
35
What 3 structures form the blood brain barrier?
- endothelial cells lining capillary wall with tight junctions between them
- astrocyte foot processes
- capillary basement membrane
36
What is unique about brain capillary endothelial cells?
Only brain capillary endothelial cells have tight junctions
37
What is the blood-CSF barrier? made of?
- prevents large molec passing from blood into CSF
| - formed by tight junctions between epithelial cells of choroid plexus
38
What are exceptions to the blood-brain barrier?
- a few special regions have fenestrated capillaries and no blood-brain barrier so molec in blood can affect brain function
- ----- area postrema --> vomiting after chemo
- ----- OVLT --> osmotic sensing
- - in neurohypophysis no BB barrier so that ADH can be released from brain into circulation
39
How much ox/glucose does brain need per minute?
500-600 ml oxygen
| 75-100 mg of glucose
40
Where does energy for brain come from?
- oxidative metabolism of glucose
41
How much time deprived of oxygen will it take for neuron to die?
5-7 minutes
42
List in order of most sensitive to anoxia (no oxygen)?
[most sensitive > least sensitive]
-- astrocyte, axon, blood vessel, microglia, myelin, nerve cell (soma), oligodendroglial cell
nerve cell > axon > myelin > oligodendroglial cell > astrocyte > microglia > blood vessel
43
What are 3 especially sensitive regions of CNS to anoxia?
- neurons in cortical layers 3 and 5
- hippocampus neurons (CA1 region, sommer's sector)
- purkinje cells of cerebellum
44
What is eosinophilic degeneration? What happens to the cytoplasm? nucleus?
- irreversible neuronal response to injury
- perikaryal cytoplasm becomes eosinophylic (bright pink + homogeneous)
- nucleus becomes pyknotic (dark and shrunken)
45
When is eosinophilic degeneration visible?
4-6 hours after injury
46
What is the axonal reaction? Histo appearance?
- follows damage to or disease of the axon
- may be reversible if integrity of axon restored
- RER disintegrates
- swelling and rounding of cell body
- disappearance of Nissl substance
- cytoplasm smooth (central chromatolysis)
- peripheral migration of nucleus
47
What is role of astroctyes in response to brain injury?
- form glial scar comprised of reactive astrocytes
48
What are the 3 steps of glial scar formation in response to brain injury
1. Astrocytosis = astrocyte proliferate
2. Reactive astrocytes form: cytoplasm swells and becomes eosinophilic
3. gliosis: glial fibers in astrocytes coalesce and form glial scar made of GFAP [glial fibrillary acidic protein]
49
Do fibrous (fibroblast) scars form in the brain in response to injury?
No --> glial scars are formed instead that are made of reactive astrocytes
50
What is role of microglia in brain injury
- proliferate and encircle degenerating neurons [neuronophagia]
- form clusters around necrotic brain tissue
- differentiate into macrophages --> go to site of damage and phagocytize debris associated with injury
51
What is role of microglia in brain injury
- proliferate and encircle degenerating neurons [neruonophagia]
- form clusters around necrotic brain tissue
- differentiate into macrophages --> go to site of damage and phagocytize debris associated with injury
52
What is cerebral edema?
- response to injury
- increased water content or abnormal distribution of water in brain parenchyma (intracellular or extracellular spaces)
- occurs with many acute pathologic processes
53
What is vasogenic edema?
- failure of tight junctions and astrocytic processes of blood brain barrier
- allows normally excluded intravascular proteins/fluid to enter cerebral parenchymal extracellular space
54
What is vasogenic edema?
- failure of tight junctions and astrocytic processes of blood brain barrier
- allows normally exluded intravascular protiens/fluid to enter cerebral parenchymal extracellular space
55
How can you treat vasogenic edema?
steroids and osmotic therapy (mannitol)
56
With what types of disease do you see vasogenic edema?
- tumors, brain abscesses, traumas, inflammation, hypertension
57
What is cytotoxic edema?
- derangement in cellular metabolism causing failure of ATP-dependent Na/Ca transport
- causes cellular retention of Na --> H20 folllows
- astrocytic processes, capillary endothelial cells, and neurons swell --> cut off cerebral perfusion to adjacent areas so further hypoxic damage --> more cyto edema --> more cerebral swelling
- can lead to potential herniation
- BBB stays intact
58
What is cytotoxic edema?
- derrangement in cellular metabolism causing failure of ATP-dependent Na/Ca transport
- causes cellular retention of Na --> H20 folllows
- astrocytic processes, capillary endothelial cells, and neurons swell --> cutt of cerebral perfusion to adjacent areas so further hypoxic damage --> more cyto edema --> more cerebral swelling
- can lead to potential herniation
- BBB stays intact
59
Does cytotoxic edema response to steroid or osmotic diuretics?
nope!
60
What diseases is cytotoxic edema associated with?
- early ischemia, hypoxia (cardiac arrest), asphyxia, various toxins
61
Where do you see cytotoxic edema fluid on imaging?
- involves astrocytes so see it in both grey and white matter
- loss of grey-white matter interphase
62
What are 5 clinical symptoms of increases intracranial pressure?
- headache
- nausea/vomiting
- bradycardia
- hypertension
- loss of consciousness
- papilledema (optic disc swelling)
63
Why should you always consider brain CT or MRI before performing an LP?
- occult CNS lesion can potentially produce herniation after LP
64
What is the Monroe Kellie doctrine?
- skull has fixed volume that contains brain/CSF/blood
- if increase volume of one, need to compensate by decrease in volume of others OR an increase in intracranial pressure will occur
65
What is equation for cerebral perfusion pressure?
CPP = MAP - ICP
| cerebral perfusion pressure = mean arterial pressure - intracranial pressure
66
What happens to CPP if high ICP (intracranial pressure)
CPP = MAP - ICP so if you increase ICP you will get lower CPP thus brain will have inadequate blood flow --> ischemia
67
What are the 4 types of herniations
- subfalcine herniation
- transtentorial (uncal) herniation
- central herniation
- cerebellar/tonsillar herniation
68
What is a subfalcine herniation?
- cingulate gyrus is pushed laterally away from
expanding mass and herniates beneath falx cerebri
- seen with frontal masses
- can compress anterior cerebral artery
69
What is an uncal transtentorial herniation?
- uncus of temporal lobe herniates down into posterior fossa through tentorial notch
- can be terminal
70
What is the uncus?
medial temporal lobe
71
What are possible signs of uncal trantentorial herniation?
- can be terminal unless ICP managed
- compresses ipsilateral (on same side) CN III --> fixed and dilated pupil and "down and out" gaze
- compress ipsilateral posterior cerebral artery --> contralateral homonymous hemianopsia = visual field loss on both eyes
- compress contralateral crus cerebri --> causes ipsilateral paralysis = false localization sign
72
What is a central herniation?
- swelling of cerebral hemispheres causes to directly herniate down and cause bilateral uncal herniation
- have sudden sever increased ICP --> can be especially lethal with young people because no room to accommodate increase brain swelling
73
WHen do you see central herniation?
- in young people with trauma, subarachnoid hemorrhage, meningitis
74
What is cerebellar/tonsillar herniation?
- tonsil of cerebellum herniates down through foramen magnum
- due to increase ICP in posterior fossa (where cerebellum + brainstem are located)
- rapidly can progress to terminal brainstem compression
75
When do you see cerebellar/tonsillar herniation?
- increased ICP in posterior fossa (cerebellum/brainstem) from mass, edema, bleed, etc)
76
Symptoms of cerebellar/tonsillar herniation?
- severe occipital headache, stiff neck, shoulder pain
- papilledema (swollen eye disc)
- rapidly causes terminal brainstem compression
77
How does CSF flow?
- produced by choroid plexus --> to lateral ventricles --> through inter-ventricular foramina --> to 3rd ventricle --> through cerebral aqueduct --> to 4th ventricle
- exits ventricle system through foramina in 4th ventricle --> enters subarachnoid space and reabsorbed by arachnoid granulations
78
What type of cells play role in inhibiting nerve regeneration?
- glial cells , axons cannot grow across glial scar
79
Can PNS regenerate?
yes!
80
Where/when does neurogenesis occur?
- mostly during pre-natal development
- recently discovered adult neurogenesis continues in hippocampus and sub-ventricular zone (lining lateral ventricles)
- hippocampal neurogenesis may be related to learning/memory, function not well known
81
What does neuronal plasticity mean?
- brain changes structurally/functionally with experience/activity
- underlies longterm learning and memory
- also mech of chronic pain and addition
82
What is long-term potentiation (LTP)?
- major mech of neuronal plasticity
| - long-lasting enhancement in signal transmission between 2 neurons resulting from stimulation them synchronously
