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Flashcards in Stroke Deck (15)
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1
Q

What is stroke?

A

Group of disorders involving haemorrhage or occlusion of blood brain vessels

2
Q

Types of stroke

A
  • Haemorrhagic
  • Ischaemic

Typically focal but can be global (i.e in cardiac arrest)

3
Q

Stroke risk factors

A

Diabetes; hypertension; atherosclerosis; polymorphisms

4
Q

Schematic of the brain following stroke

A

The area where the stroke has occured (greatest loss of blood flow) is the core/infarct and die by rapid necrosis.
Area around it where nerve cells have been deprived of some oxygen is the penumbra where cells die slower, typically by apoptosis

5
Q

What are the potential causes for delayed cell death (penumbra region, thus target area?)

A
  • Glutamate release (massive)
  • influx of Ca2+
  • Free radicals
  • microglia activation
  • apoptotic mechanisms
6
Q

What is the excitotoxicity theory?

A

excess activation of glutmate systems in the brain causes cell death

7
Q

What are the glutamate receptors in the brain

A

1) ionotropic: AMPA;Kainate; NMDA

2) Metabotropic- G protein linked

8
Q

AMPA receptors

Link to stroke

A

LGIC

Causes Na+ influx. Has many subunits GluR1-4.If has Glur2 sodium, if 3, Calcium. Injury can cause downregualtion of 2.

9
Q

Kainate receptors

A

GluR5-7

LGIC, causes Na+ influx

10
Q

NMDA receptors

how do they work

role of Mg2+

A

Is a ligand and voltage gated channel
Depolarisation+ glutamate and glycine bonding opens the channel causes calcium influx, depolarisation.

Mg2+ occupies and blocks channel, however when depolarised, efflux of it. Hence voltage dependent.

11
Q

What is significant about the PCP binding site on the NMDA receptor?

A

PCP (angel dust) binds to a sub unit and blocks the channel. making it a (non competitive) antagonist of the NMDA receptor. Typically NMDA antagonists are neuroprotective (stop large influx of calcium)

12
Q

What are the two types of metabotropic glutmate receptors?

A

Group 1- mGluR1 and 5: activate phospholipae C, then IP3 and DAG to release calcium from intracellular stores, depolarise. Antagonists are neuroprotective typically.

Group 2- mGluR2 and 3: Gi linked, Inhibit adenylate cyclase and stop NT release. Agonsist can be neuroprotective

13
Q

Theory on the ions causing harm in stroke and the time associated with the receptors (hypothesis)

A

Calcium influx, in turn by NMDA receptors responsible for penumbric region woth apoptotic cell death over hours to days. Calcium causes activation of calcium sensitive enzymes then apoptosis e.g. caspase 3

Na+ influx due to AMPA and Kainate receptors will cause the rapid cell death and necrosis at the core/infarct area

14
Q

What treatments can we use for stroke?

A

TPA for ischaemic strokes, for thrombolysis. Must be given within a few hours (short time) after stroke to work.

Glutamate antagonists have failed due to complex nature of NMDA receptor.

15
Q

How can targeting other brain cells be beneficial?

A
  • Astrocytes involved in neuroprotection so may want to target these
  • Pericytes and endothelial cells to re-establish blood flow i.e promoting angiogenesis