Ahmad Saif, Elsherbiny Nehal M, Haque Rizwanul, Khan M Badruzzaman, Ishrat Tauheed, Shah Zahoor A, Khan Mohammad M, Ali Mehboob, Jamal Arshad, Katare Deepshikha Pande, Liou Gregory I, Bhatia Kanchan
Department of Biological Sciences, Rabigh College of Science and Arts, King Abdulaziz University (Jeddah), P.O. Box 344, Rabigh 21911, Kingdom of Saudi Arabia.
Department of Clinical Biochemistry, Mansoura University, Mansoura, Egypt.
Neurotoxicology. 2014 Dec;45:100-10. doi: 10.1016/j.neuro.2014.10.002. Epub 2014 Oct 12.
Stroke is a severe neurological disorder characterized by the abrupt loss of blood circulation into the brain resulting into wide ranging brain and behavior abnormalities. The present study was designed to evaluate molecular mechanism by which sesamin (SES) induces neuroprotection in mouse model of ischemic stroke. The results of this study demonstrate that SES treatment (30 mg/kg bwt) significantly reduced infarction volume, lipid per-oxidation, cleaved-caspase-3 activation, and increased GSH activity following MCAO in adult male mouse. SES treatment also diminished iNOS and COX-2 protein expression, and significantly restored SOD activity and protein expression level in the ischemic cortex of the MCAO animals. Furthermore, SES treatment also significantly reduced inflammatory and oxidative stress markers including Iba1, Nox-2, Cox-2, peroxynitrite compared to placebo MCAO animals. Superoxide radical production, as studied by DHE staining method, was also significantly reduced in the ischemic cortex of SES treated compared to placebo MCAO animals. Likewise, downstream effects of superoxide free radicals i.e. MAPK/ERK and P38 activation was also significantly attenuated in SES treated compared to placebo MCAO animals. In conclusion, these results suggest that SES induces significant neuroprotection, by ameliorating many signaling pathways activated/deactivated following cerebral ischemia in adult mouse.
中风是一种严重的神经紊乱疾病，其特征是脑部血液循环突然丧失，导致广泛的脑部和行为异常。本研究旨在评估芝麻素（SES）在缺血性中风小鼠模型中诱导神经保护的分子机制。本研究结果表明，在成年雄性小鼠大脑中动脉闭塞（MCAO）后，SES治疗（30 mg/kg体重）显著降低了梗死体积、脂质过氧化、裂解的半胱天冬酶-3激活，并增加了谷胱甘肽（GSH）活性。SES治疗还减少了诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）蛋白表达，并显著恢复了MCAO动物缺血皮层中超氧化物歧化酶（SOD）活性和蛋白表达水平。此外，与安慰剂MCAO动物相比，SES治疗还显著降低了包括离子钙结合衔接分子1（Iba1）、NADPH氧化酶2（Nox-2）、COX-2、过氧亚硝酸盐在内的炎症和氧化应激标志物。通过二氢乙锭（DHE）染色法研究发现，与安慰剂MCAO动物相比，SES治疗组缺血皮层中的超氧自由基产生也显著减少。同样，与安慰剂MCAO动物相比，SES治疗组中超氧自由基的下游效应即丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）和p38激活也显著减弱。总之，这些结果表明，SES通过改善成年小鼠脑缺血后激活/失活的许多信号通路，诱导显著的神经保护作用。
