Reduction of ischemic damage in NGF-transgenic mice: Correlation with enhancement of antioxidant enzyme activities

If permanent focal ischemia is induced by middle cerebral artery occlusion (MCAO), neurons within the infarcted territory die by necrosis and apoptosi s (or programmed cell death). We have previously shown, using a mouse strai n transgenic (tg) for the nerve growth factor (NGF) gene, that tg mice have consistently smaller infarcted areas than wild-type (wt) animals, correlat ed with upregulated NGF synthesis and impaired apoptotic cell death. We stu died, in wt and tg mice subjected to MCAO, the activities of several antiox idant enzymes and the synthesis of the proteins of the Bcl-2 family. Our re sults show that the antiapoptotic Bcl-2 protein and glutathione peroxidase are recruited after MCAO. NGF-tg mice also had an intrinsic resistance to o xidative stress because their basal copper zinc superoxide dismutase (SOD) and glutathione transferase activities were high. Additionally, manganese S OD activity increased in NGF-tg mice after MCAO, correlating strongly with the resistance of these mice to apoptosis. (C) 1999 Academic Press.