Pathophysiology of cerebral ischemia.

The purpose of this manuscript is to briefly review the pathophysiology of cerebral ischemia. Ischemic thresholds are well-defined in lower animals. The concept of the ischemic penumbra may include regions of brain around deeper regions of ischemia but has also been defined in terms of brain salvageable by reperfusion or by pharmacological therapies. The principal pathophysiological processes in cerebral ischemia are energy failure, loss of cell ion homeostasis, acidosis, increased intracellular calcium, excitotoxicity, and free radical-mediated toxicity. The underlying biochemical processes are similar regardless of the amount of brain that is made ischemic or the duration of ischemia. The relative contributions of each process are believed to vary significantly especially in relation to the level of cerebral blood flow. Neurons may die by necrosis or apoptosis. In the core of an infarct where blood flow is very low, the predominant process is energy failure and rapid necrotic cell death. Reperfusion of ischemic tissue produces an influx of inflammatory cells and of oxygen that can cause increases in oxygen-derived free radicals. Free radicals are also important in prolonged ischemia. There is interest in changes in gene expression after ischemia. Induction of heat shock proteins suggests that gene expression changes may protect neurons from death. Changes in gene expression also may initiate apoptosis or other detrimental processes. Although advances have been made, there are still no proven pharmacological therapies to rescue ischemic human neurons. Such therapies do appear to be on the horizon.