The biochemical basis of ischemic brain lesions.
A major mechanism leading to ischemic damage is loss of cellular ion homeostasis. Energy failure with shortage of ATP is responsible for presynaptic release of glutamate, which then triggers rapid cellular efflux of K+, and influx of Ca2+, Na+, and Cl-, with osmotically obligated water. The neuronal damage occurring in ischemia is probably secondary to the influx of Ca2+, and/or to the intracellular release of Ca2+, with the subsequent activation of proteases and lipases. A delayed form of ischemic damage, observed after transient ischemia, may be caused by increased calcium cycling across metabolically perturbed membranes. Another type of damage, typically leading to pan-necrosis (infarction), seems related to excessive acidosis and to production of free radicals. The mechanisms may involve release of pro-oxidant iron-catalyzed free radical reactions. It has been proposed that free radical damage may preferentially affect microvessels, predisposing to vasogenic edema.
Siesjö
B K
BK
Laboratory for Experimental Brain Research, University of Lund, Sweden.
Smith
M L
ML
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000502:physiology; D004734:Energy Metabolism; D005609:Free Radicals; D006801:Humans
D005609:Free Radicals; D002118:Calcium