[Neuronal death mechanisms in cerebral ischemia].
BACKGROUND
Morphological and biochemical studies have shown an apoptotic component in neurons following either focal or global ischemia in adults, or hypoxia-ischemia during development.


METHODS
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.
Ferrer
I
I
Unidad de Neuropatología, Hospital Príncipes de España, Bellvitge, España. iferrer@sakma.es
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002545:Brain Ischemia / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D019254:Genes, bcl-2 / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D014158:Transcription, Genetic / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor
Mecanismos de muerte neuronal en la isquemia cerebral.