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

<p>Mitochondria are known targets of ischemia-reperfusion injury in adult brain. Although neonates are more resistant to ischemic episodes, the mechanisms accounting for this are not yet fully understood. The aim of this study therefore was to determine whether a difference in post-ischemic mitochondrial function may play a role in the heightened recovery of the neonatal brain following ischemia-reperfusion. We have therefore compared the effects of an in vitro model of ischemia on the enzymes of the mitochondrial respiratory chain in isolated nerve terminals (synaptosomes) from neonatal and adult rats. Ischemia caused a significant, reversible decrease in mitochondrial Complex I activity in both adult and neonatal preparations. In neonatal preparations alone, ischemia also led to a significant decrease in mitochondrial Complexes II-III activity. Following 30 min of reperfusion mitochondrial Complexes II-III and IV exhibited decreased activity in synaptosomes from adult, but not neonatal rats. These data suggest a difference in the susceptibility of adult as compared to neonatal nerve terminal mitochondria to ischemia-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 the adult brain. This adds to the growing body of evidence that mitochondrial function plays a key role in neuronal death following cerebral ischemia reperfusion.</p>