Cerebrovascular function - Ian Winship Flashcards
What does the circle of willis have?
Collateral vasculature
Do capillaries have smooth mm.?
No; but can have pericytes
What is an ischemic stroke
85% of strokes due to blockage of a cerebral vessel
What are the two forms of ischemic stroke?
Thrombic –> area of vessel irritated, thus forming clots; thromboembolic –> clot travels from somewhere else
What is an hemorrhagic stroke?
Rupture of blood vessel
Is mortality greater for H. stroke?
Yes, 40-50% early mortality in subarachnoid hem.
What is subarachnoid hem caused by?
Raised intracranial pressure, vasospasm (constriction of blood vessels for days, thus also causing I.stroke)
Describe intracerebral hemorrhage stroke?
Vessels ruptures leaking blood into parenchyma, thus causing mechanical disruption and blood toxicity; more common with hypertension diabetes due to stiff BV
What type of arteries are commonly affected in intracerebral hem?
lenticolostriate arteries as they are connected to high-pressure BV
What is the stroke core and penumbra?
Stroke core: tissue dies immediately where vessel ruptures; penumbra is surrounding and doesn’t die immediately due to BV collaterals
How does stroke initiate ischemic cascade?
no blood = decrease ATP –> acidosis (anaerobic compensation) –> failure of Na/K pumps –> mem. depolarization –> glutamate excitotoxicity —> increase Ca+ leading to necrotic + apoptotic cell death
What does capsase 3 mean?
Apoptosis (programmed cell death)
What does LC3 and Beclin 1 mean?
Repair/recycling processes are impaired (autophagy)
What does pycnotic cells mean?
Necrosis at stroke core (rapidly depolarizing and lysing cells)
What are pannexins? (panx)
Panx are large pore channels that indescrimnantly lets things in (positive ions come in and stay in)
What does blocking panx do?
Stops anoxic depolarization; however, injury comes within minutes so its hard to block panx at right time
Describe the extrinsic pathway in apoptosis?
Receptor activation leads to activation of caspase 8, thus activating caspase 3
Describe the intrinsic pathway in apoptosis?
Mitochondrial stress opens MPTP, releases Cytochrome C, activates caspase 9 and then activates caspase 3
What is the apoptosis induced factor (AIF)?
Regulates cascade-independent pathway in apoptosis (no caspase 3)
Where does apoptosis occur?
Outside of stroke core, in pneumbra
What is diaschisis?
Area of NS connected with injured area shows decreased metabolism due to loss of reciprocal connections that maintain neural activity
Does diaschisis show atrophy?
Yes
Describe focal diaschisis at rest?
Decreased energy metabolism
Describe focal diaschisis while functioning?
Abnormalities in metabolism and neuronal activity
Describe connectional diaschisis?
Selective change in coupling between two notes of a defined network, involves areas distant from lesion
Describe connectional diaschisis?
Change in structural and functional connective, including disconnection/reorganization of subgraphs (includes all connections in brain and is mostly theoretical )
What is GAP-43?
Growth associated protein found in axonal cores that helps with spinal plasticity after stroke
How does the corticospinal tract (CST) regulate stroke outcome?
increased integrity increases motor performances/recovery
Has amyloid been found in stroke hemispheres and is it important?
Yes, can cause secondary Neurodegeneration; hasn’t been studied much, thus no evidence of amyloid as a key mediator
What causes delayed schema in Subarachnoid Hem. stroke?
Vasospams; overall cause cognitive impairment
What commonly causes global schema?
Heart attacks
Which area of the brain is particularly susceptible to global ischemia?
CA1 (important in learning/memory)
What are the characteristics of chronic hypo perfusion?
Researchers cut of Common carotid, thus only leaving anterior circulation;
Overall, reduced blood flow, reduced cognition and reduced in hippocampal volume. However, no motor symptoms
What does hypo perfusion do mechanism wise?
Oxidative stress; hypoxia; inflammation
Importantly, it causes endothelial dysfunction which impairs auto regulation. There is also BBB breakdown which leads to influx of more damaging factors.
What does the BBB breakdown lead to?
- accumulation of toxic factors, like thrombin
- Faulty transport thus decrease in LRP1 (amyloid effluxer), increase in RAGE (amyloid influxer)
- RBC lysing, microbleeds, Fe+
- Inflammation etc
what is the neurovascular unit?
Various cells regulating blood flow; pericyte, endothelium, basement membrane, microglia, astrocyte, oligodendrocyte, neuron
What are the mechanisms of vascular dementia?
- Microbleed/microinfarcts
- hypoperfusion
- small vessel ATS, arteriosclerosis, deposit of fat in vessel –> all narrow BVs
- ALL CASES LEAD TO NARROW BVs and HYPOERFUSION
What are the types of vascular dementia?
- Multi infaract (most common) step wise progression
- Strategeic (focal): large vessel occlusion; never return to normal but can be slightly improved
- White matter hyperintensity (atrophy based progression - steadier)
What is the vascular hypotehsis in AD
Interaction bewteen A beta and vascualr risk factrs lead to impaired processing and AD pathology
Is cerebrovascular function impaired in AD?
Yes
APOE4 has greater risk
What is cerebral amyloid angiopathy?
Deposition of amyloid in** blood vessels** rather than brain; key contributor to cog. decline; causes hypoperfusion, white matter intesntiy,** perivascular space**; inflammation etc
Describe the ischemic and hemorrhagic pathway in CAA:
- Ischemia: Desposition of amyloid in BV-> impaired vasodilation (reactivity) and activity in brain -> microinfarcts, etc
- Hem. : loss of **vascular integrity **–> rupture —> iron accumulation / symptomic hemorrhage (intracerebral hemorrhage)
Can CAA patients increase Blood flow?
No; not able to increase blood flow in resposne to specific challenge
Is cerebrovascular reactivity impaired in CAA?
Yes, so are AD and MCI; however, CAA more impacted than AD and MCI
