[Molecular factors of cerebral hypoxia-ischemia].
In recent years much has been learned about the cellular and molecular events underlying cerebral hypoxia-ischemia (HI). We review, from a molecular standpoint, the main pathogenetic theories in hypoxic-ischemic cerebral injury, including excitotoxicity, free radical damage, and the role of growth factors, proto-oncogenes and heat shock proteins. The various forms of cell death in the developing and adult brain (necrosis, apoptosis and delayed neuronal death) are reviewed, with an emphasis on gene regulation of naturally-occurring and HI-associated cell death. We report the expression of the immediate early gene c-fos and c-jun mRNAs and of HSP72 mRNA and protein in several models of cerebral HI. Gel agarose electrophoresis of extracted DNA and in situ end-labeling of fragmented DNA revealed that cell death in these models was associated with endonuclease(s) activation. We also pre-treated some animals with dexamethasone, a neuroprotective drug in a model of perinatal HI. High-dose dexamethasone prevented c-fos induction in cerebral regions sensitive to HI. This effect may be due to a functional antagonism, at the transcriptional level, between Fos and the glucocorticoid receptor.
Macaya
A
A
Secció de Neurología Infantil, Hospital Vall d'Hebron, Barcelona.
Munell
F
F
Reventós
J
J
Ferrer
I
I
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000503:physiopathology* / Q000648:ultrastructure*; D002545:Brain Ischemia / Q000503:physiopathology*; D016923:Cell Death; D003907:Dexamethasone / Q000494:pharmacology; D004720:Endonucleases / Q000502:physiology; D005609:Free Radicals; D000860:Hypoxia / Q000503:physiopathology*; D009414:Nerve Growth Factors / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000648:ultrastructure; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects / Q000648:ultrastructure; D012333:RNA, Messenger / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D005609:Free Radicals; D009414:Nerve Growth Factors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D004720:Endonucleases
Factores moleculares en la hipoxia-isquemia cerebral.