Stroke & Excitotoxicity

Question 1

What is a stroke?

Answer 1

Transient or permanent interruption in cerebral blood supply, leading to ischaemia (lack of oxygen and glucose).

Question 2

What is exctitotoxicity?

Answer 2

Excessive glutamate release overstimulates neurons, leading to calcium overload, oxidative stress, and cell death.

Question 3

Name the key ionotropic glutamate receptors involved in excitotoxicity. (4)

Answer 3

AMPA, Kainate (KA), and NMDA receptors

Question 4

What happens in Stage 1 of excitotoxicity (3)

Answer 4

• AMPA/KA receptors cause Na⁺ influx.
• NMDA receptors cause Na⁺ and Ca²⁺ influx.
• Depolarisation is regulated by voltage-gated ion channels.

Question 5

What triggers Stage 2 of excitotoxicity?

Answer 5

• Na⁺/K⁺ pump failure due to lack of oxygen/glucose.
• Excess extracellular K⁺ and intracellular Na⁺ → Depolarisation.
• Increased glutamate release and Ca²⁺ influx.

Question 6

What is peri-infarct depolarisation?

Answer 6

Repeated depolarisation in penumbra neurons causing energy depletion and excitotoxic cell death.

Question 7

What is peri-infarct depolarisation?

Answer 7

Repeated depolarisation in penumbra neurons causing energy depletion and excitotoxic cell death

Question 8

What is reperfusion injury?

Answer 8

Sudden restoration of oxygen/blood flow after ischaemia causing reactive oxygen species (ROS) production and further damage.

Question 9

What is the primary treatment for ischaemic stroke?

Answer 9

Tissue Plasminogen Activator (tPA): A clot dissolving agent effective within 3 hours of stroke onset.

Question 10

Why is tPA contraindicated in haemorrhagic stroke?

Answer 10

It can worsen bleeding and increase damage.

Question 11

Name neuroprotective strategies under investigation for stroke (5)

Answer 11

• Glutamate receptor blockers
• Glutamate release blockers
• Sodium/calcium channel blockers
• Free radical scavengers
• Protease and caspase inhibitors

Question 12

What are transient ischaemic attacks (TIAs)?

Answer 12

“Mini-strokes” with temporary neurological symptoms; often a precursor to a full stroke.

Question 13

What are common secondary prevention strategies for stroke? (4)

Answer 13

1. Antihypertensives: Lower blood pressure
2. Statins: Lower cholesterol
3. Antiplatelet Drugs: Prevent clotting (e.g., aspirin).
4. Lifestyle Changes: Improve diet, exercise, stop smoking.

Question 14

What are some long-term symptoms of stroke? (3)

Answer 14

• Motor deficits
• Cognitive impairment
• Emotional and behavioural changes

Question 15

Name examples of neurodegenerative diseases linked to excitotoxicity (4).

Answer 15

1. Alzheimer’s
2. Parkinson’s
3. Huntington’s
4. ALS (Motor Neurone Disease) [aka ice bucket challenge]

Question 16

What is amnesic shellfish poisoning?

Answer 16

Excitotoxicity caused by glutamate receptor agonists in contaminated shellfish.

Symptoms: confusion, memory loss, seizures, and death.

Question 17

What is neurolathyrism?

Answer 17

Motor neuron degeneration caused by glutamate agonists in the grass pea (Lathyrus Sativus).

Question 18

What is Guam Disease?

Answer 18

A condition by Beta-Methylamino-L-alanine from cycad seeds via bats, resulting in symptoms of motor neuron disease, Alzheimer’s, and Parkinson’s.

Question 19

How does oxidative stress contribute to excitotoxicity?

Answer 19

ROS produced during reperfusion cause DNA damage, lipid peroxidation, and further neuronal death.

Question 20

What role do calcium ions play in excitotoxicity?

Answer 20

Excessive Ca²⁺ influx activates enzymes and free radicals that lead to cells damage and death.