In the early phase of cerebral ischemia,factors threatening neuronal survival in the penumbra include mainly glutamate excitotoxicity,free radical damage and energy failure resulting from recurrent depolarization wave...In the early phase of cerebral ischemia,factors threatening neuronal survival in the penumbra include mainly glutamate excitotoxicity,free radical damage and energy failure resulting from recurrent depolarization waves.However,at later times,other mechanisms come into play.The initial ischemic event activates a variety of genetic programs that unfold over the course of hours and days.Both positron emission tomography and magnetic resonance based techniques demonstrate that the development of irretrievable tissue damage is relatively slow,progressing over the course of several days in some cases,and a viable tissue,defined by hemodynamic and metabolic criteria,is still present many hours after stroke in human or in monkey.These findings suggest that the brain can potentially be“rescued”from infarction many hours after onset of ischemia and challenge the widespread notion of an early and short“therapeutic window”(~3-6h).This realization is of critical importance for stroke therapy because most patients reach medical attention at a time when current therapeutic strategies may no longer be effective.Therefore,it would be highly desirable to develop therapeutic interventions that can be instituted many hours after the onset of ischemia.We believe that addressing the mechanisms of delayed cell death is key to a successful therapy.The studies presented here were designed to document the potential contribution of apoptosis to ischemia induced neuronal death.We will discuss the morphological,biochemical and pharmacological evidence for apoptosis in the ischemic stroke.展开更多
文摘In the early phase of cerebral ischemia,factors threatening neuronal survival in the penumbra include mainly glutamate excitotoxicity,free radical damage and energy failure resulting from recurrent depolarization waves.However,at later times,other mechanisms come into play.The initial ischemic event activates a variety of genetic programs that unfold over the course of hours and days.Both positron emission tomography and magnetic resonance based techniques demonstrate that the development of irretrievable tissue damage is relatively slow,progressing over the course of several days in some cases,and a viable tissue,defined by hemodynamic and metabolic criteria,is still present many hours after stroke in human or in monkey.These findings suggest that the brain can potentially be“rescued”from infarction many hours after onset of ischemia and challenge the widespread notion of an early and short“therapeutic window”(~3-6h).This realization is of critical importance for stroke therapy because most patients reach medical attention at a time when current therapeutic strategies may no longer be effective.Therefore,it would be highly desirable to develop therapeutic interventions that can be instituted many hours after the onset of ischemia.We believe that addressing the mechanisms of delayed cell death is key to a successful therapy.The studies presented here were designed to document the potential contribution of apoptosis to ischemia induced neuronal death.We will discuss the morphological,biochemical and pharmacological evidence for apoptosis in the ischemic stroke.
