Lixisenatide ameliorates cerebral ischemia-reperfusion injury via GLP-1 receptor dependent/independent pathways

Comparable to pentoxiphylline; both doses of lixisenatide produced a significant reduction in infarct volume and amelioration of neurobehavioural functions along with suppression of oxidative stress parameters (catalase, reduced glutathione, malondialdehyde and NO), inflammatory marker (tumor necrosis factor-alpha) and apoptotic marker (caspase-3) in ischemic rat brains. However, these effects weren'tinhibited by GLP-1R antagonist, exendin(9−39), indicating that they are independent on GLP-1R mediation. Also, lixisenatide upregulated protein expression of cerebral endothelial nitric oxide synthase and the angiogenic marker, vascular endothelial growth factor. It's worth noting that this effect was blocked by exendin(9−39). Overall, these data indicated that lixisenatide may offer a promising approach for alleviating cerebral I/R injury via different mechanisms that could be mediated, in part, through GLP-1R.