Heightened resistance of the neonatal brain to ischemia-reperfusion involves a lack of mitochondrial damage in the nerve terminal

Mitochondria are known targets of ischemia-reperfusion injury in adult brai n. Although neonates are more resistant to ischemic episodes, the mechanism s accounting for this are not yet fully understood. The aim of this study t herefore was to determine whether a difference in post-ischemic mitochondri al function may play a role in the heightened recovery of the neonatal brai n following ischemia-reperfusion. We have therefore compared the effects of an in vitro model of ischemia on the enzymes of the mitochondrial respirat ory chain in isolated nerve terminals (synaptosomes) from neonatal and adul t rats. Ischemia caused a significant, reversible decrease in mitochondrial Complex I activity in both adult and neonatal preparations. In neonatal pr eparations alone, ischemia also led to a significant decrease in mitochondr ial Complexes II-III activity. Following 30 min of reperfusion mitochondria l Complexes II-III and IV exhibited decreased activity in synaptosomes from adult, but not neonatal rats. These data suggest a difference in the susce ptibility of adult as compared to neonatal nerve terminal mitochondria to i schemia-reperfusion. These data show for the first time that nerve terminal mitochondria from immature animals remain undamaged following a period of ischemia and reperfusion, in contrast to nerve terminal mitochondria from t he adult brain. This adds to the growing body of evidence that mitochondria l function plays a key role in neuronal death following cerebral ischemia r eperfusion. (C) 1999 Elsevier Science B.V. All rights reserved.