Cerebrovascular function - Ian Winship

Question 1

What does the circle of willis have?

Answer 1

Collateral vasculature

Question 2

Do capillaries have smooth mm.?

Answer 2

No; but can have pericytes

Question 3

What is an ischemic stroke

Answer 3

85% of strokes due to blockage of a cerebral vessel

Question 4

What are the two forms of ischemic stroke?

Answer 4

Thrombic –> area of vessel irritated, thus forming clots; thromboembolic –> clot travels from somewhere else

Question 5

What is an hemorrhagic stroke?

Answer 5

Rupture of blood vessel

Question 6

Is mortality greater for H. stroke?

Answer 6

Yes, 40-50% early mortality in subarachnoid hem.

Question 7

What is subarachnoid hem caused by?

Answer 7

Raised intracranial pressure, vasospasm (constriction of blood vessels for days, thus also causing I.stroke)

Question 8

Describe intracerebral hemorrhage stroke?

Answer 8

Vessels ruptures leaking blood into parenchyma, thus causing mechanical disruption and blood toxicity; more common with hypertension diabetes due to stiff BV

Question 9

What type of arteries are commonly affected in intracerebral hem?

Answer 9

lenticolostriate arteries as they are connected to high-pressure BV

Question 10

What is the stroke core and penumbra?

Answer 10

Stroke core: tissue dies immediately where vessel ruptures; penumbra is surrounding and doesn’t die immediately due to BV collaterals

Question 11

How does stroke initiate ischemic cascade?

Answer 11

no blood = decrease ATP –> acidosis (anaerobic compensation) –> failure of Na/K pumps –> mem. depolarization –> glutamate excitotoxicity —> increase Ca+ leading to necrotic + apoptotic cell death

Question 12

What does capsase 3 mean?

Answer 12

Apoptosis (programmed cell death)

Question 13

What does LC3 and Beclin 1 mean?

Answer 13

Repair/recycling processes are impaired (autophagy)

Question 14

What does pycnotic cells mean?

Answer 14

Necrosis at stroke core (rapidly depolarizing and lysing cells)

Question 15

What are pannexins? (panx)

Answer 15

Panx are large pore channels that indescrimnantly lets things in (positive ions come in and stay in)

Question 16

What does blocking panx do?

Answer 16

Stops anoxic depolarization; however, injury comes within minutes so its hard to block panx at right time

Question 17

Describe the extrinsic pathway in apoptosis?

Answer 17

Receptor activation leads to activation of caspase 8, thus activating caspase 3

Question 18

Describe the intrinsic pathway in apoptosis?

Answer 18

Mitochondrial stress opens MPTP, releases Cytochrome C, activates caspase 9 and then activates caspase 3

Question 19

What is the apoptosis induced factor (AIF)?

Answer 19

Regulates cascade-independent pathway in apoptosis (no caspase 3)

Question 20

Where does apoptosis occur?

Answer 20

Outside of stroke core, in pneumbra

Question 21

What is diaschisis?

Answer 21

Area of NS connected with injured area shows decreased metabolism due to loss of reciprocal connections that maintain neural activity

Question 22

Does diaschisis show atrophy?

Answer 22

Yes

Question 23

Describe focal diaschisis at rest?

Answer 23

Decreased energy metabolism

Question 24

Describe focal diaschisis while functioning?

Answer 24

Abnormalities in metabolism and neuronal activity

Question 25

Describe connectional diaschisis?

Answer 25

Selective change in coupling between two notes of a defined network, involves areas distant from lesion

Question 26

Describe connectional diaschisis?

Answer 26

Change in structural and functional connective, including disconnection/reorganization of subgraphs (includes all connections in brain and is mostly theoretical )

Question 27

What is GAP-43?

Answer 27

Growth associated protein found in axonal cores that helps with spinal plasticity after stroke

Question 28

How does the corticospinal tract (CST) regulate stroke outcome?

Answer 28

increased integrity increases motor performances/recovery

Question 29

Has amyloid been found in stroke hemispheres and is it important?

Answer 29

Yes, can cause secondary Neurodegeneration; hasn’t been studied much, thus no evidence of amyloid as a key mediator

Question 30

What causes delayed schema in Subarachnoid Hem. stroke?

Answer 30

Vasospams; overall cause cognitive impairment

Question 31

What commonly causes global schema?

Answer 31

Heart attacks

Question 32

Which area of the brain is particularly susceptible to global ischemia?

Answer 32

CA1 (important in learning/memory)

Question 33

What are the characteristics of chronic hypo perfusion?

Answer 33

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

Question 34

What does hypo perfusion do mechanism wise?

Answer 34

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.

Question 35

What does the BBB breakdown lead to?

Answer 35

* 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

Question 36

what is the neurovascular unit?

Answer 36

Various cells regulating blood flow; pericyte, endothelium, basement membrane, microglia, astrocyte, oligodendrocyte, neuron

Question 37

What are the mechanisms of vascular dementia?

Answer 37

* Microbleed/microinfarcts * hypoperfusion * small vessel ATS, arteriosclerosis, deposit of fat in vessel --> all narrow BVs * **ALL CASES LEAD TO NARROW BVs and HYPOERFUSION**

Question 38

What are the types of vascular dementia?

Answer 38

* 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)

Question 39

What is the vascular hypotehsis in AD

Answer 39

Interaction bewteen A beta and vascualr risk factrs lead to impaired processing and AD pathology

Question 40

Is cerebrovascular function impaired in AD?

Answer 40

Yes ## Footnote APOE4 has greater risk

Question 41

What is cerebral amyloid angiopathy?

Answer 41

Deposition of amyloid in** blood vessels** rather than brain; key contributor to **cog. decline**; causes **hypoperfusion**, white matter intesntiy,** perivascular space**; inflammation etc

Question 42

Describe the ischemic and hemorrhagic pathway in CAA:

Answer 42

* 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)

Question 43

Can CAA patients increase Blood flow?

Answer 43

No; not able to increase blood flow in resposne to specific challenge

Question 44

Is cerebrovascular reactivity impaired in CAA?

Answer 44

Yes, so are AD and MCI; however, CAA more impacted than AD and MCI