Lecture 5: Excitotoxicity

Question 1

What are three things vital to normal function?

Answer 1

EAA Neurotransmitter System
Calcium
Oxygen

Question 2

After ischemia in the brain, there is an overstimulation of the EAA system. Broadly speaking, what is it responsible for?

Answer 2

Damage to neurons even if they are not in ischemic site

Question 3

What happens to cells after a stroke?

Answer 3

Without oxygen, in four minutes ATP production stops and the Na/K ATPase activity decreases, leading to a depolarization of the cell membrane. (Cell is more positive than normal).
This depolarization leads to many action potentials, releasing NT (specifically EAA) all over the brain.

Question 4

Why can’t glial cells reuptake the EAA?

Answer 4

Requires secondary active transport of Na+

Question 5

What happens with so much EAA in the synaptic cleft?

Answer 5

Huge influx of calcium into the post-synaptic cells

Question 6

What are the four consequences of high intracellular calcium?

Answer 6

1. Increase in Phospholipase A: Damage cell membrane
2. Activation of μ-calpain: Damage to cell structure
3. Activation of calcineurin: Increase of Nitric Oxide
4. Activation of apoptotic pathway: Cell death

Question 7

What are some specific consequences of an increase in Phospholipase A?

Answer 7

Proteins are unfolded and no longer being made

Mitochondria issues

Question 8

How is the apoptotic pathway initiated?

Answer 8

Mitochondria releases Caspase 9 which activates pro-apoptotic Caspase 3

Question 9

Why is it not a good idea to introduce oxygen back in after ischemia?

Answer 9

Damaged mitochondria cannot properly utilize oxygen. This forces the oxygen to become free radicals, exacerbating the problem