Excitotoxicity Flashcards
How can non-local neurons be damaged in a brain injury event?
Over-stimulation of the EAA system, no way to reuptake EAAs, activates non-NMDA receptors which allows Ca2+ to enter post-synaptic cells
Why is high intracellular calcium dangerous?
Increases phospholipase A activity which acts on membrane to release arachadonic acid (part of cell membrane = damaged) which becomes a second messenger.
Also activates mu-calpain (proteolytic enzyme) which degrades structural enzymes and decreases protein synthesis = impairs neurons
Also activates calcineurin which produces excess NO
Also activates apoptotic pathway (caspase 3)
What can happen with reperfusion?
Free radicals due to impaired ability of mitochondria to use O2
Further activation of caspase 3 due to some mitochondria producing ATP which was used to phosphorylate a kinase
