J. Keelan et al., Heightened resistance of the neonatal brain to ischemia-reperfusion involves a lack of mitochondrial damage in the nerve terminal, BRAIN RES, 821(1), 1999, pp. 124-133
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.