Lecture 5: Stroke

Question 1

What is stroke?

Answer 1

clinical presentation of a discrete episode where there is injury of the brain because of a vascular event (occlusion of a vessel or haemorrhage)

Question 2

Describe the blood supply to the brain

Answer 2

Anterior brain (bulk of cerebral hemispheres) supplied by: common and internal carotid arteries

Posterior brain (posterior parts of cerebral hemispheres, occipital lobe, brainstem and cerebellum) supplied by: two vertebral arteries that converge to form the basilar artery (the vertebra-basilar system)

Question 3

What is the middle cerebral artery?

Answer 3

the single biggest territory on either side in terms of cerebral hemispheres - most commonly affected artery in stroke cases

Question 4

What is the circle of willis?

Answer 4

formed of the middle cerebral arteries and the basilar artery
- joins the anterior and posterior circulations

Question 5

What is tPA?

Answer 5

tissue plasminogen activator (removes clots)

Question 6

What heart rhythm defect can give a very high stroke risk?

Answer 6

atrial fibrillation

Question 7

What is the epidemiology of stroke?
(prevalence and what stroke is associated with)

Answer 7

the most prevalent neurological disorder under 85 years of age

associated with:
increased long-term mortality
physical, cognitive and behavioural impairments
recurrent stroke
increased risk of other vascular events such as MI

Question 8

What are the three main types of stroke?

Answer 8

80% Ischaemic stroke (typically caused by blockage in large artery - but can be small arteries as well)

15% primary intracerebral haemorrhage - related to high blood pressure, cerebral amyloid angiopathy (beta-amyloid plaques in vessel walls)

5% subarachnoid haemorrhage (spontaneous most often linked to intercranial aneurysms but also traumatic SAH)

Question 9

What are the causes of ischaemic stroke?

Answer 9

atherotheomboembolism (such as carotid artery disease - ultrasound scans show narrowing of the carotid artery)

Intracranial small-vessel disease (perforating vessels deep within the vein - small lacuna infarct)

cardiac embolism (atrial fibrillation, undiagnosed hole in heart in younger stroke cases)

Question 10

What is a hemicraniectomy?

Answer 10

removal of part of the skull to allow the brain sweeling (oedema) to occur through this space and relieve pressure on other brain structures

Question 11

What are non-modifiable risk factors of stroke?

Answer 11

family history (genetics)
age
gender
race

Question 12

What are modifiable risk factors of stroke?

Answer 12

hypertension
diabetes
smoking
hypercholesterolaemia
atrial fibrillation

Question 13

How do risk factors increase propensity to stroke?

Answer 13

• promote atherosclerosis and stiffening of arteries
• induce narrowing, thickening of arterioles and capillaries
  –> this leads to reduced cerebral blood flow and alterations in regulation of cerebral blood flow.
  –> ability of endothelium to regulate microvascular flow is compromised so get a mismatch been the brains energy supply and demand

Question 14

How do risk factors affect cerebral blood vessels?

Answer 14

increased production of ROS and promotion of inflammation in systemic and cerebral blood vessels

Oxidative stress related to biological inaction of nitric oxide by free radical superoxides reduces NO bioavailability and prevents its beneficial effects leading to loss of vasoregulatory effects, anti-aggregant effects, anti-proliferative and anti-cell adhesion effects

Question 15

What are some stroke triggers?

Answer 15

rupture of atherosclerotic plaque
thrombosis
systemic infection
pregnancy and puerperium - venous stroke - venous sinus thrombosis
illicit drugs

Question 16

What is the difference between the ischaemic core zone and and the ischaemic penumbra?

Answer 16

Ischaemic core zone = area of severe ischaemia, loss of oxygen and glucose resulting in rapid depletion of energy stores, rapid neuronal death and supporting cellular elements (glial cells)

Ischaemic penumbra = area adjacent to core zone that receives intermediate blood flow and is less affected = ischaemia but still viable cerebral tissue - not gone to infarct

Question 17

What does the energy deficit (loss of oxygen and glucose) in severe ischaemia result in?

Answer 17

intracellular ionic imbalance
mitochondrial failure
activation of intracellular proteases, lipases and ribonucleases
–> leads to rapid breakdown of cellular structural elements and loss of cellular integrity

Question 18

Where are pharmacologic interventions most likely to be effective in stroke cases?

Answer 18

the penumbra (reduced perfusion but still some from collateral arteries) - but cells in this area will eventually die if reperfusion is not established in early hours so hence why this is the main target area for treatment
(cells within the core zone are rarely salvageable)

Question 19

How does excitotoxicity occur in stroke events?

Answer 19

uncontrolled release of glutamate from depolarising or dying neurons
- activation of glutamate receptors NMDA and AMPA
- leads to uncontrolled extracellular calcium influx and dysregulation of intracellular calcium homeostasis
- results in generation of ROS and nitrogen species, mitochondrial dysfunction, activation of apoptosis

Question 20

What is the effect of acute ischaemic stroke (AIS) on the blood brain barrier?

Answer 20

BBB breaksdown after AIS and may lead to oedema and haemorrhage transformation (bleeding into the infarcted area)

Question 21

How does breakdown of BBB relate to clinical outcomes?

Answer 21

breakdown of BBB is associated with poorer clinical outcomes due to exacerbation of brain injury

Question 22

What are some mediating factors of BBB breakdown after AIS?

Answer 22

inflammatory processes
formation of ROS
activation of matric metalloproteinase-9 (MMP-9)

Question 23

Why do Alzheimer’s disease and cerebrovascular disease often co-exist?

Answer 23

deposition of beta amyloid in blood vessels in AD (amyloid angiopathy)