[Neuronal death mechanisms in cerebral ischemia]

Abstract

Introduction: Morphological and biochemical studies have shown an apoptotic component in neurons following either focal or global ischemia in adults, or hypoxia-ischemia during development.

Development: Different factors, including transcription factors, members of the Bcl-2 family, caspases and trophic factors, participate in the cascade of events leading to cell death. Transcription factor c-Jun is induced and expressed in the three models of ischemia as a non-specific response to the ischemic stress. The role played by the different members of the Bcl-2 family is not clear in cerebral ischemia. It is feasible that Bcl-2 expression is not sufficient to protect nerve cells from dying in those animals with physiological dotations of this protein. Yet Bcl-xS may have a role in ischemia-induced cell death following global ischemia in the adult or hypoxia-ischemia during development. Recent studies have also shown a similar putative role of caspase 1 and caspase 3 following cerebral ischemia. Finally, the ischemic insult is usually accompanied by modifications in the expression of neurotrophins and receptors.

Conclusions: Brain-derived neurotrophic factor (BDNF) administration preserves nerve cells from dying following focal or global ischemia in adults, and hypoxia-ischemia during development. This positive effect is probably dependent on the cross-signaling between BDNF and its specific receptor TrkB. Cumulative evidence in experimental models indicates BDNF as a putative agent in the treatment of cerebral ischemia in humans.