Evidence that p38 mitogen-activated protein kinase contributes to neonatal hypoxic-ischemic brain injury

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.