Dexamethasone prevents apoptosis in a neonatal rat model of hypoxic-ischemic encephalopathy (HIE) by a reactive oxygen species-independent mechanism

It has previously been shown, in a neonatal rat model of hypoxic-ischemic encephalopathy (HIE), that neuronal injury can be attenuated by pretreatment with dexamethasone. The mechanism by which dexamethasone exerts this protective effect is not known. Using the same neonatal rat model of HIE, we fou...

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Bibliographic Details
Published in:Brain research 1997-01, Vol.747 (1), p.9-17
Main Authors: Ekert, Paul, MacLusky, Neil, Luo, Xiao Ping, Lehotay, Denis C, Smith, Barry, Post, Martin, Tanswell, A.Keith
Format: Article
Language:English
Subjects:
Aldehydes - metabolism
Animals
Animals, Newborn - physiology
Anti-Inflammatory Agents - pharmacology
Apoptosis - drug effects
Blotting, Northern
Brain
Brain Chemistry - drug effects
Brain Ischemia - metabolism
Brain Ischemia - pathology
Cell death
Dexamethasone - pharmacology
DNA - drug effects
Hypoxia, Brain - metabolism
Hypoxia, Brain - pathology
Lipid peroxidation
Lipid Peroxidation - drug effects
Peroxynitrite
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Proto-Oncogene Proteins c-fos - biosynthesis
Rats
Rats, Wistar
Reactive oxygen species
Reactive Oxygen Species - metabolism
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Summary:It has previously been shown, in a neonatal rat model of hypoxic-ischemic encephalopathy (HIE), that neuronal injury can be attenuated by pretreatment with dexamethasone. The mechanism by which dexamethasone exerts this protective effect is not known. Using the same neonatal rat model of HIE, we found pretreatment with dexamethasone to have no effect on the generation of superoxide radical, products of lipid peroxidation, peroxynitrite-mediated tissue damage or bcl-2 protein expression. However, dexamethasone did inhibit the induction of c-fos transcription seen following HIE, and subsequent evidence of apoptosis. We conclude that it is possible to limit hypoxic-ischemic neuronal injury, despite the continued production of reactive oxygen species, by interventions which block the cascade of events culminating in apoptosis. The involvement of apoptosis in the neuronal injury of HIE, if confirmed in acutely asphyxiated human infants, suggests that there may be a post-injury `window of opportunity' for neuroprotective interventions.
ISSN:0006-8993
1872-6240
DOI:10.1016/S0006-8993(96)01201-2