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 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.
Ekert
P
P
Neonatology Division, Hospital for Sick Children, Toronto, Ont., Canada.
MacLusky
N
N
Luo
X P
XP
Lehotay
D C
DC
Smith
B
B
Post
M
M
Tanswell
A K
AK
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D001923:Brain Chemistry / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D004247:DNA / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D002534:Hypoxia, Brain / Q000378:metabolism / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000447:Aldehydes; D000893:Anti-Inflammatory Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D017382:Reactive Oxygen Species; D003907:Dexamethasone; D004247:DNA