Stroke Flashcards
(53 cards)
Why study white matter damage?
White matter contains nerve fibers that are vunreble to damage in stroke
Define Ischemia
inadequate oxygen or blood supply to an organ
Define stroke
sudden loss of brain function due to a disruption in blood flow or bleeding in the brain.
Define oxidative stress
a condition where there’s an imbalance in the body, with an excess of reactive oxygen species (free radicals) and insufficient antioxidants to neutralize them
Define Necroptosis
a regulated caspase independent form of cell death that shares morphological and inflammatory characteristics with an unregulated, passive form of cell death called necrosis
Mitochondria can supports…
necroptotic signalling.
How many synapses are glutaminergic?
85%
What NT kills neruons in Grey matter?
Glutamate
glutamate receptor antagonist block neuronal death
Define Anoxia
complete lack of oxygen supply to a tissue or organ- severe form of hypoxia
What does anoxia/Ischemia cause
+ what will this look like on a NT v Time graph
Dramatic rise in glutamate
You see a dramatic increase of glutamate release on graph, attempt at recovery then increase
How is glutamate removed from synapse
Removed quickly by uptake carriers in glail cells.
This is very important for the ability to have quick thoughts where glutamate release is very transient.
What happens to glutamate uptake in stroke
Reversed uptake so glutamte is pumped out instead of taken in by uptake carriers
Which extraceullar ions increase during stroke?
Postassium
Glutamate
Which extraceullar ions decrease during stroke?
Sodium
Reverse uptake so its being pumped into cell so increase intracelluar sodium
Which intraceullar ion increase during stroke?
Calcium
Increase calcium into cell
calcium overload activates enzymes that release glutamate=excitotoxicity.
During stroke, What happens with loss of ATP supply in glial cells
Na/K pump is no longer able to pump sodium ions out and potassium ions back in.
The potassium now accumulates in extracellular space and sodium ions are not being pumped out
Together, this causes a depolarizing effect = excitoxicity
What model was used to detect reverse glutamate uptake? (Billups & Attwell,1996) B&A
Electrogenic glutamate transport was
studied in whole-cell clamped glial (Muller) cells isolated from the
salamander retina
Which cells uptake glutamate to maintain homestasis?
astrocyte glial cells
What is glutamate uptake powered by
transmembrane gradients of sodium, potassium and pH.
Why did B&A block AMPA/KA receptors
This was to show that blocking AMPA receptors and glutamate receptors does something to depolarization.
What happened when PDC was applied to muller cells (B&A)?
Antagnist for glutamate receptor
Causes current measuremnt to decrease
If stroke is occuring and current is being recorded, how would we know glutamate reverse uptake is the reason for early stroke?
Measure current then apply glutamte blocker, you see a small decrease in current, proves glutamate release is invovled in early stroke. Still see some current because reuptake transports still letting glutamte out from glail cells.
How can you test glutamte reuptake is the reason for early stroke?
Patch clamp experiements
Block specifically reuptake receptors using PCD- causes no release of glutamte= no chnage in current is seen
How did they use hippocampal slices to detect glutamate release duirng stroke
*Voltage clamp hippocampal CA1 pyramidal cells at –30mV
*Expose slices to solution mimicking ischaemia
*Monitor membrane current generated by pyramidal cell
