• Huiqing Liu, Xinbing Wei, Lin Chen, Xiaoqian Liu, Senpeng Li, Xinyong Liu, and Xiumei Zhang.
• Department of Pharmacology, School of Medicine, Shandong University, Jinan, PR China.
• Pharmacology. 2013 Jan 1; 92 (3-4): 198-206.

AimsThis study was conducted to investigate the protective effects of CXC195, a tetramethylpyrazine analogue, in acute focal cerebral ischemia/reperfusion (I/R) injury in rats and to elucidate the potential mechanism.MethodsMiddle cerebral artery occlusion for 2 h followed by reperfusion for 24 h was conducted in male Wistar rats and different doses of tetramethylpyrazine and CXC195 were intraperitoneally injected at 30 min after reperfusion.ResultsOur results demonstrated that CXC195 at the dosage of 3 and 10 mg/kg significantly reduced the neurological deficit score and the infarct volume compared to the vehicle-treated group. In addition, CXC195 exhibited a protective effect against hippocampus neuronal cell death and significantly restored the brain ATP content. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidative capability (T-AOC), as well as production of malondialdehyde (MDA) and reactive oxygen species (ROS) were assayed in ipsilateral hemisphere homogenates to evaluate the redox status after I/R injury. Treatment with CXC195 significantly attenuated the decrease of SOD, GPx and T-AOC activities and inhibited the elevation of MDA content and ROS generation. Furthermore, CXC195 prevented the upregulation of the NADPH oxidase (NOX) 2 and NOX4, and reduced inducible nitric oxide synthase (iNOS) induction and production of nitric oxide induced by I/R.ConclusionThese results suggest that CXC195 has a neuroprotective effect in transient focal ischemia, which is most likely due to its antioxidant activity by inhibiting NOX and iNOS expression.© 2013 S. Karger AG, Basel.

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