Mechanisms of Acute Neuronal Injury

Question 1

Two causes of neuron death during acute injury

Answer 1

Excitotoxicity and cytotoxic edema

Question 2

(A) cause for excitotoxicity

Answer 2

Ecessive accumulation of glutamate in the extracellular space causes excitotoxicity. Patholical over activation of NMDA type glutamate receptors -> intracellular calcium overload

Question 3

Similarities between NMDA/AMPA receptors

Answer 3

• Glutamate binding

* Permeable to Na+ and K+

Question 4

Differences between NMDA/AMPA receptors

Answer 4

• NMDA permeable to Ca2+
• NMDA requires glutamate and glycine for gating
• NMDA receptors contain binding sites for Mg2+ and other ions/drugs in pore

Question 5

Why is synaptic glycine not necessarily to gate NMDA receptors?

Answer 5

Extracellular fluid normally has low concentration of glycine. Binding site is high affinity.

So influx of glutamate usually does the damn job.

Question 6

Pharmacological importance of pore binding sites of NMDA receptors

Answer 6

It’s a target for dissociative anesthetics. Ketamine is used for pain management. Dextromethorpha/dextrorphan used as a cough syrup. ÖKSÜRÜK ŞURUBU

Question 7

Two scenarios in which cell volume regulation is impaired

Answer 7

1) ATP stores are depleted (active pumps knocked out)

2) membrane ion permeability becomes high (hello excitotoxicity we meet again)

Question 8

Consequences of Ca2+ overload in the cell

Answer 8

1) abnormal activation of lipases, proteases
2) free radical production
3) cell membrane damaged by lipid and protein degradation, lipid peroxidation

Question 9

Chronic neurodegenerative diseases which excitotoxicity may contribute to

Answer 9

Amyotrophic lateral sclerosis (ALS), Huntington’s disease, and Alzheimer’s disease