Cerebral ischemia and reperfusion: the pathophysiologic concept as a basis for clinical therapy.

The ischemic penumbra has been documented in the laboratory animal as severely hypoperfused, nonfunctional, but still viable brain tissue surrounding the irreversibly damaged ischemic core. Saving the penumbra is the main target of acute stroke therapy, and is the theoretical basis behind the reperfusion concept. In experimental focal ischemia, early reperfusion has been reported to both prevent infarct growth and aggravate edema formation and hemorrhage, depending on the severity and duration of prior ischemia and the efficiency of reperfusion, whereas neuronal damage with or without enlarged infarction also may result from reperfusion (so-called reperfusion injury). Activated neutrophils contribute to vascular reperfusion damage, yet posthypoxic cellular injury occurs in the absence of inflammatory species. Protein synthesis inhibition occurs in neurons during reperfusion after ischemia, underlying the role that these pathways play in prosurvival and proapoptotic processes that may be differentially expressed in vulnerable and resistant regions of the reperfused brain tissue. Ischemia-induced decreases in the mitochondrial capacity for respiratory activity probably contribute to the ongoing impairment of energy metabolism during reperfusion and possibly also the magnitude of changes seen during ischemia. From these experimental data, the concept of single-drug intervention cannot be effective. Further experimental research is needed, especially of the study of biochemical markers of the injury process to establish the role of several drugs.