Stroke Flashcards
(75 cards)
1
Q
What is a stroke?
A
brain damage and dysfunction that results from reduction in blood flow to the brain
2
Q
What is the difference between stroke and ischemia?
A
- stroke occurs in the brain
- ischemia occurs in the vascular system
- stroke results from brain ischemia
3
Q
What percentage of strokes are ischemic vs hemorrhagic?
A
- ischemic = 85%
- hemorrhagic = 15%
4
Q
What is a hemorrhagic stroke?
A
rupture of blood vessel in the brain
5
Q
TRUE or FALSE: hemorrhagic has a higher mortality rate than ischemic stroke
A
TRUE
6
Q
What are the 2 types of hemorrhagic strokes?
A
- subarachnoid hemorrhage (SAH)
- intracerebral hemorrhage (ICH)
7
Q
What are the symptoms of SAH?
A
- bleeding in subarachnoid space
- raised intracranial pressure due to blood trapped in subarachnoid space
- vasospasm
8
Q
What can vasospasm due to SAH cause?
A
contraction of vessels to restrict blood flow –> global ischemia –> death
9
Q
What are symptoms of ICH?
A
- vessel ruptures leaking blood into parenchyma –> blood toxicity
10
Q
Which arteries are often affected in ICH?
A
lenticolostriate arteries
11
Q
Which conditions are ICH common with?
A
hypertension and diabetes
12
Q
What does global ischemic stroke result from? focal ischemic stroke?
A
- global results from reduced blood flow to the entire brain –> HEART ATTACK
- focal results from occlusion of a vessel in the brain - typically MCA –> THROMBUS, EMBOLUS
13
Q
What do stroke symptoms depend on?
A
size and location, which depends on vasculature: occluded vessel vs collateral blood supply
14
Q
What is another name for proximal occlusions of the middle cerebral artery? Does it cause cortical or striatal damage? What are some symptoms to look for?
A
- M1 occlusion
- cortical and striatal damage
- symptoms: hemiparalysis, aphasia
15
Q
What is another name for distal occlusions of the MCA? Does it cause cortical or striatal damage? What are some symptoms to look for?
A
- M2 occlusion
- cortical damage only
- symptoms: more focal neurological signs
16
Q
Why are the lenticulostriate arteries prone to ruputre?
A
they are very fragile and there is high pressure at M1; therefore a big pressure gradient
17
Q
What kind of symptoms do lacunar infarcts lead to?
A
silent symptoms
18
Q
What is the normal perfusion rate? ischemic perfusion rate when cells irreversibly die? ischemic perfusion rate when cells are silent but alive?
A
- normal: 50 mL/100g/min
- irreversible ischemia: <10 mL/100g/min
- silent but alive ischemia: <20 mL/100g/min
19
Q
TRUE or FALSE: there is better blood flow closer to the occlusion.
A
FALSE: there is better blood flow farther from the occlusion
20
Q
What kind of arteries maintain partial blood flow in a stroke? Is partial blood flow associated with a stroke core or penumbra?
A
pial collaterals; penumbra
21
Q
Summarize the ischemic cascade.
A
- loss of aerobic metabolism
- loss of ATP , acidosis
- Na/K-ATPase failure
- depolarization
- excitotoxicity
- increase in intracellular Na+, Ca2+, Cl-
- cytotoxic edema
- protease activation
- free radicals
- lipid peroxidation
- mitochondrial failure (MPTP)
- immune cell infiltration and inflammation
- apoptosis
22
Q
Why do depolarizations cause ischemia?
A
- ANOXIC (because loss of blood flow)
- peri-infarct depolarizations increase metabolic demand (stressful for cells)
23
Q
How is edema cytotoxic?
A
H2O follows ions into the cell –> swelling –> rupture
24
Q
Describe excitotoxicity in terms of ischemia.
A
release of glutamate, activation of signaling pathways and further depolarization (feedforward mechanism)
25
In ischemic stroke, which transporter proteins fails, causing loss of Cl- gradient? Does this cause or inhibit inhibition? How does this affect intracellular levels of Na+, Ca2+ and Cl-?
- KCC2 failure
- impair inhibition
- increased intracellular levels of Na+, Ca2+, and Cl-
26
Describe the signaling cascade that results from a change in intracellular ion concentrations and receptor activation?
- protease activation
- free radical generation
- lipid peroxidation
- mitochondrial failure
- necrosis and apoptosis
27
damage to which structure of the brain allows infiltration of immune cells? activation of which cells lead to inflammation?
- damage BBB
- activate glial cells
28
TRUE or FALSE: panx stops anoxic depolarization
FALSE: BLOCKING panx stops anoxic depolarization
29
Describe extrinsic apoptosis in the peri-infarct.
1. TNF and FasR
2. Fas-associated protein with Death Domain (FADD)
3. death inducing signaling complex (DISC = R, FADD, Cas8)
4. effector caspases (Cas3)
30
Describe intrinsic apoptosis in the peri-infarct.
1. mitochondrial release of cytochrome C
2. activate Cas3
31
Draw a graph demonstrating the growth of infarct over time. Label when the following have the most impact: excitotoxicity, apoptosis, inflammation, peri-infarct depolarizations
- excitotoxicity at minutes
- peri-infarct depolarizations at minutes
- inflammation at hours/days
- apoptosis after days
(slide 14)
32
After a stroke, asevere M1 occlusion can lead to degeneration in which spinal tract?
CST
33
What is diachisis?
metabolic dysfunction
34
TRUE or FALSE: focal stroke effects do not extend outside of the core
FALSE: focal stroke effects extend outside of the core
35
Why does a cortical stroke lead to diaschisis in the cerebellum?
there are strong connections between the cerebellum and the cortex
36
TRUE or FALSE: a corrtical stroke in one area can lead to diaschisis in functionally connected cortical areas
TRUE
37
TRUE or FALSE: cell death in the penumbra is immediate, but dell death in the core offers hope for neuroprotection.
FALSE: cell death in core is immediate, penumbra offeres hope for neuroprotection
38
What are the 2 main ways to prevent damage due to ischemia? Which is best?
1. restore blood flow (best)
2. interfere with ischemic cascade
39
What is the mean time to complete a CT scan?
less than 1 hour
40
What kind of scan is used to determine if a stroke is ischemic or hemorrhagic?
CT
41
What has been the major focus for restoring blood flow after stroke over the last 20 years?
thrombolysis / clot busting
42
What is endovascular therapy?
catheter used to physically pull out clot
43
What are 3 strategies to restore blood flow after stroke?
- thrombolysis
- endovascular therapy
- collateral blood flow therapeutics
44
How does thrombolysis work?
- blood clots are made up primarily of platelets and fibrin
- recombinant tissue PLASMINOGEN activator (rt-PA) works by cleaving fibrin --> breaking up blood clots (note: PLASMIN cleaves fibrin)
45
What is the only FDA approved clinically proven treatment for acute stroke?
rt-PA (thrombolysis)
46
What scale is used to measure functional independence after rtPA tratment of stroke? what score represnets no disability to slight disability?
modified Rankin score; 0-2
47
Why does tPA worsen the stroke if it is administered after 4.5 hours?
ischemic stroke is verly likely to become hermhorragic
48
should we memorize the limitation fo rt-PA?
slide 21
49
What are newer iterations of rt-PA?
tenecteplase and desmoteplase
50
What is the window of time for endovascular therapy to be effective?
up to 24 hours after stroke
51
What is the window of time for rt-PA to be effective?
4.5 hours
52
What substance is used to increase collateral blood flow to treat stroke?
nitric oxide dependent vasodilators:
- ACh
- bradykinin
- Substance P
- adenosine
53
L-arginine vs inhaled NO vs NO donors to treat stroke?
- L-arginine: no precursor --> systemic effect
- inhaled NO: potent vasodilation, some evidence for neuroprotection
- NO donors: potent but non-selective vasodilators --> systemic effect
54
How does NO treat stroke? mechanism?
- NO increases cGMP cause vasorelaxation
- dilates all blood vessels in body (incl brain) --> restore blood flow using the collaterals
55
What are some NO donors?
- sodium nitroprusside
- nitroglycerin
56
What is arguable they best form of NO administration? Why?
- inhaled NO
- increases CBF during stroke
- treatment decreases penumbra, increasing normal perfusion
57
What kind of neuroprotective agents have been investigated for stroke treatment? Why have almost all neuroprotective agents failed to treat stroke?
- glutamate antagonists
- gltamate release inhibitors
- free radical scavengers
- Ca2+ chelators
- GABA agonists
- rushed trials
58
TRUE or FALSE: pannexins prevent anoxic depolarizations
FALSE: pannexins CAUSE anoxic depolarizations and ischemic cell death
59
Which receptor is the key driver of excitation and cell death? Do the channels have to open to cause cell death?
- NMDAR
- dont have to oepn to drive cell death
60
What are the steps for pannexins and ischemic cell death?
1. NMDAR
2. Panx
3. mPTP
61
What leads to cell death cascades?
metabotropic coupling of NMDARs to Pannexin-1
62
What are NMDA coupled via?
Src family kinases
63
How do we interfere with the cell death siognalling in a stroke?
- blocking the interaction of NMDA with Src
- block anoxic depolarization
- prevents panx1 opening and reduces damage and disability due to stroke
64
How is NA1 used to treat stroke?
- NA1 prevents PSD-95 interaction with NMDA and nNOS
- this leads to generation of NO
- NO leads to vasodilation/relaxation, notably in the collaterals
65
Label the pathophysiology of stroke over time on a graph. list the bad and good outcomes over minutes, hours, days, weeks
BAD:
- minutes: energy failure, excitotoxicity, depolarizations, necrosis
- hours-days: secondary damage (inflammation, programmed cell death)
- weeks: complications
GOOD:
- minutes/hours/days: endogenous brain protection - collaterals, GABA, anti-inflammatory cytokines, trophic factors
- days/weeks: plasticity/regeneration/repair - axonal sprouting, synaptogenesis, neurogenesis, angiogenesis, remyelination, functional remapping
(slide 31)
66
when is the best to to do rehab training after a stroke?
immediately after the injury because plasticity is at its peak, but then it decreases with time post-stroke
67
What is the 3 step model for rehabilitative scheduless?
1. IMAGING: determination of the metabolic and PLASTIC status of the brain
2. APPLICATION OF GROWTH AND PLASTICITY PROMOTING FACTORS: enhancement of the plastic status of the brain and spinal cord --> SPROUTING FIBERS
3. REHAB TRAINING: selection and STABILIZATION of newly formed functional connections
68
Which protein peaks the most in the post-stroke cervical spinal cord? What is it associated with in terms of stroke recovery?
- Gap43
- when gap43 increases, axonal sprouting increases (i.e. Gap43 associated with spinal plasticity)
69
after a stroke, at what day does axonal sprouting end? What does this imply about recovery?
- axonal sprouting ends at 28 days
- this means the window for functional recovery also ends at 28 days
70
TRUE or FALSE: the uninjured side of the brain in a stroke can rewire and cross over at the spinal cord
TRUE
71
What is the main barrier for axonal growth after stroke? What is the mechanism?
CSPGs - act on receptors NgR1, NgR3, RPTP
(therefore, if we get rid of CSPGs, we can promote axonal sprouting)
72
TRUE or FALSE: CSPGs are downregulated by injury
FALSE: upregulated
73
Why does sprouting and plasticity stop at 35 days?
bc there is an increase in CSPGs
74
What is one way to get rid of CSPGs?
- Chondroitinase ABC (ChABC) cleaves GAG chains from CSPGs
- enhances plasticity and plasticity
75
TRUE or FALSE: using only rehab can allow near full recovery after stroke
FALSE: both rehab and getting rid of CSPGs is necessary for good recovery --> INDUCES SECOND WAVE OF POST-STROKE RECOVERY
