Abstract
We tested the response of stress-activated mitogen-activated protein kinases (MAPKs) - p38 MAPK and c-JUN NH2-terminal kinase (JNK) - following hypoxia-ischemia (H-I) induced by unilateral carotid artery ligation and hypoxia (8% O2 and 92% N2) for 2.5 h in postnatal-day-7 rats. Phosphorylation of p38 MAPK increased in the hippocampus and cortex immediately following H-I and returned to a basal level 6 h later. In contrast to p38 MAPK, phosphorylation of JNK decreased in the hippocampus and cortex immediately following H-I. Intracerebroventricular administration of two different p38 MAPK inhibitors prior to H-I significantly protected the neonatal brain from H-I injury. Interestingly, p38 MAPK inhibitors did not attenuate caspase-3 activation 24 h after H-I. Thus, these data suggest that p38 MAPKs contribute to the rapid, early component of brain injury following neonatal H-I.
Copyright 2002 S. Karger AG, Basel
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Blotting, Western
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Brain / drug effects*
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Brain / enzymology
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Brain / pathology
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Caspase 3
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Caspases / drug effects
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Caspases / metabolism
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / pharmacology
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Hypoxia-Ischemia, Brain / enzymology*
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Imidazoles / administration & dosage
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Imidazoles / pharmacology
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Injections, Intraventricular
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism*
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Neuroprotective Agents / administration & dosage
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Neuroprotective Agents / pharmacology
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Phosphorylation
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Pyridines / administration & dosage
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Pyridines / pharmacology
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Rats
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Rats, Sprague-Dawley
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p38 Mitogen-Activated Protein Kinases
Substances
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Enzyme Inhibitors
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Imidazoles
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Neuroprotective Agents
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Pyridines
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Casp3 protein, rat
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Caspase 3
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Caspases
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SB 203580