Reduction in oxidative stress by SOD1 overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt ⁄ GSK3β survival signaling

Abstract

Recent studies have revealed that oxidative stress has detrimental effects on central nervous system disorders including subarachnoid hemorrhage (SAH). However, how oxidative stress affects acute brain injury after SAH remains unknown. In this study, we investigated the relationship between oxidative stress and acute brain injury after SAH using SOD1 transgenic (Tg) rats. SAH was produced by endovascular perforation in wild-type (Wt) and SOD1 Tg rats. Apoptotic cell death at 24 h, detected by a cell death assay, was significantly decreased in the cerebral cortex of the SOD1 Tg rats compared with the Wt rats. The mortality rate at 24 h was also significantly decreased in the SOD1 Tg rats. A hydroethidine study demonstrated that superoxide anion production after SAH was reduced in the cerebral cortex of the SOD1 Tg rats. Moreover, phosphorylation of Akt and glycogen synthase kinase-3β (GSK3β), which are survival signals in apoptotic cell death, was more enhanced in the cerebral cortex of the SOD1 Tg rats after SAH using Western blot analysis. These results suggest that reduction in oxidative stress by SOD1 overexpression may attenuate acute brain injury after SAH via activation of Akt/GSK3β survival signaling, which could be the therapeutic target of clinical SAH.