44. CVD/Neuro

Question 1

Define

Peroxynitrite

Answer 1

a powerful oxidant exhibiting a wide array of tissue damaging effects, including lipid peroxidation, inactivation of enzymes and ion channels via protein oxidation and nitration, and inhibition of mitochondrial respiration

Question 2

Definition

a powerful oxidant exhibiting a wide array of tissue damaging effects, including lipid peroxidation, inactivation of enzymes and ion channels via protein oxidation and nitration, and inhibition of mitochondrial respiration

Answer 2

Peroxynitrite

Question 3

How do immune cells enter the brain following stroke?

Answer 3

Stroke causes BBB damage causing it to become leaky

Stroke causes an increase in sympathetic output

Activates lymphoid organs - release immune cells

Immune cells migrate throughout the body – affect systemic organs

Question 5

How do the immune cells that enter the brain following stroke cause more damage?

Answer 5

Release of cytokines

Question 6

How soon after stroke does immune cells in the brain peak?

Answer 6

24 hours after

Question 7

What happens to infarct volume when T and B cells are unable to get into the brain?

Answer 7

Reduced volume

Question 8

Where do the leukocytes that enter the brain following stroke come from?

Answer 8

Minor lymphoid organs (i.e. bone marrow) initially and then the spleen

Question 9

How do we know that the spleen is the source of the immune cells that enter the brain following stroke?

Answer 9

Animals with a splenectomy have less infact damage

Spleen decreases in size post stroke

Question 10

If apoptosis in the spleen starts at 24 hours following stroke, why doesn’t the spleen decrease in size until 72 hours?

Answer 10

The cells that died due to apoptosis aren’t fully cleared until 72 hourss

Question 11

Why is raised blood pressure common after stroke?

Answer 11

Reduced acetylcholine-mediated vasodilation

Question 12

Ischaemic stroke decreases acetycholine-mediated dilation in the mesenteric artery but does not alter sodium nitroprusside-mediated dilation in the mesenteric artery. What does this mean?

Answer 12

The receptor is unaffected by the stroke. The issue must be upstream in the acetylcholine pathway

Question 13

What does the decreased nitric oxide following stroke cause in the endothelium?

Answer 13

Leukocytes adhere to endothelial cells and release ROS

Increased ROS causes scavenges NO

Superoxide that scavenges NO forms peroxynitrite (highly damaging oxidant)

Question 14

Stroke increases immune cell infiltration within the Brain as soon as _______ after onset

Answer 14

Stroke increases immune cell infiltration within the Brain as soon as 6 h after onset

Question 15

How does stroke trigger the release of immune cells from lymphoid tissue?

Answer 15

Increased sympathetic output

Question 16

How does stroke cause endothelial vascular dysfunction?

Answer 16

Increased superoxide production

Question 17

What percentage of seizures is caused by stroke in the elderly?

Answer 17

50%

Question 18

What percentage of stroke survivors do seizures occur in?

Answer 18

9%

Question 19

What type of stroke is more likely to result in seizures?

Answer 19

Haemorrhagic

Question 20

Why is stroke more likely in people with epilepsy?

Answer 20

Treatment with enzyme-inducing AEDs, such as Phenytoin, is significantly associated with increased blood levels of total cholesterol, atherogenic (non-HDL) cholesterol, triglycerides.

Long-term AED therapy may result in low-grade systemic inflammation and increase in oxidative stress

In both cohorts who did not present with any comorbidities, the patients in the epilepsy cohort exhibited a 3-fold increased stroke risk