Retigabine attenuates focal cerebral ischemic injury through inhibiting mitochondria-dependent apoptotic pathway.

Abstract

We explored the protective effect of retigabine (RTG) on focal cerebral ischemic injury and the potential molecular mechanism. A mouse model of middle cerebral artery occlusion (MCAO) was established to induce cerebral ischemic injury. Blood samples were collected for the measurement of malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH). The brain infarct volume was stained by triphenyltetrazolium chloride. The cell apoptosis was observed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining. The expression of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), cleaved caspase 3, p-p38 and p-JNK, were determined by Western blot. RTG treatment reduced the MCAO-induced increase in brain infarct volume and neurological deficit scores. RTG treatment reduced the level of MDA and increased the activity of SOD and GSH. RTG treatment also decreased the Bax/Bcl-2 ratio and cleaved caspase 3 expression in the ischemic tissues. Further, RTG treatment decreased the phosphorylation levels of p38 and JNK in the ischemic tissues. RTG attenuated cerebral ischemic injury through reducing oxidative stress and mitochondria-mediated apoptosis via inhibiting p38 and JNK phosphorylation.