[Death/survival signaling pathways in cerebral ischemia and the developing therapeutic strategies]

In an aging society, the incidence of brain ischemia increases dramatically. Despite progress in pathophysiology mechanisms, the medical therapy for brain ischemia has not been satisfactory. Recanalization using tissue plasminogen activator only modestly improves patient outcome, and inhibiting excitotoxicity has shown no clinical benefit. Both do not provide an adequate time window for effective stroke therapy in clinical practice. A more reasonable therapeutic window, and hence a greater potential for clinical success, is likely to be attained by placing emphasis on ameliorating the effects of the synergistic processes of programmed cell death (PCD) that is active for hours to days after ischemia. It is necessary to identify molecular mediators of ischemic neuroprotection suitable for translation to human clinical trials. In this review, the mechanisms of cell death/survival signaling pathways after ischemia and the potential therapeutic targets will be discussed.