Stroke

Question 1

What is a stroke?

Answer 1

Ischemic - blockage of blood vessels by a thrombus

or haemorrhagic - rupture of blood vessels.

Question 2

What are the different regions in the brain caused by a stroke/

Answer 2

Core infarct - cells die from necrosis
Penumbra - delayed cell apoptosis (24-72 hours)
Surrounded by normal brain activity.

Question 3

What are the causes for cell death within the penumbra?

Answer 3

Massive release of glutamate - saturation of transporters out of synapse. Causes excessive activation of glutamate systems, including pathological activation of NMDA and AMPA receptors.

Glutamate activates NMDA receptores, which
causes an influx of intracellular Ca2+ ions resulting in delayed nerve cell death via apoptosis in the penumbra via activation of the apoptotic caspase cascade.

Glutamate alsoactivates the AMPA receptors which cause rapid nerve cell dealth via cell lysis and necrosis in the core.

Free raidcal production
Activation of brain, macrophages and microglia releasing NO, superoxide, cytokines
Activation of apoptotic mechanisms.

Question 4

What are the types of glutamate receptors?

Answer 4

Ligand gated ion channels - AMPA and Kainate (Na influx)
NMDA - ion channel

Metabotropic - G protein coupled receptor

Question 5

Describe NMDA receptors.

Answer 5

Requires voltage depolarisation, and glutamate and glycine binding.
Allows Ca2+ to enter the cell.
PCP section inside the channel is bound by angel dust and it blocks the receptor

Question 6

Describe the metabotropic glutamate receptor.

Answer 6

Group 1 - G-protein coupled receptor. Activates phospholipase C and depolarises neurons.

Glutamate binds - IPS/DAG > increase calcium from intracellular stores and increase in protein kinase C

Group 2: inhibits adenylate cyclase and causes inhibition of neurotransmitter release

Question 7

What are the treatments of Stroke

Answer 7

TPA - not for haemorrhages