Yu Guo, Wu Fei, Wang Er-Song
Department of Neurosurgery, Jinshan Hospital, Fudan University Shanghai 201500, People's Republic of China.
National Engineering Laboratory for Anti-tumor Protein Therapeutics, Qinghua University Beijing 100000, People's Republic of China.
Int J Clin Exp Pathol. 2015 Feb 1;8(2):1213-25. eCollection 2015.
Stroke is one of the three diseases that cause human death in current world, and it is the common, frequently occurring disease in the middle-old ages. NMDA receptors mediate glutamate-induced cell death when intensely or chronically activated, which is an important cause of neuronal cell death after acute injuries. Here, we demonstrated that BQ-869, a potent NMDA receptor antagonist, blocked NMDA receptor in concentration-dependent and dose-dependent manner, attenuated NMDA-induced Ca(2+) influx, inhabited NMDAR-mEPSC in hippocampal pyramidal neurons, improved athletic ability of rats with MACO, decreased infarction size in focal cerebral ischemia rats and reduced stroke mortality. Taken together, our data demonstrate the neuroprotective effect of BQ-869 might be through inhibiting NMDA-mediated excitotoxicity. These findings indicate that BQ-869 is the most potent antagonist of NMDA receptors, and provide new insights with potential therapeutic applications for the treatment of stroke.
中风是当今世界导致人类死亡的三大疾病之一，是中老年人群中的常见多发病。NMDA受体在受到强烈或慢性激活时介导谷氨酸诱导的细胞死亡，这是急性损伤后神经元细胞死亡的一个重要原因。在此，我们证明了强效NMDA受体拮抗剂BQ-869以浓度和剂量依赖性方式阻断NMDA受体，减弱NMDA诱导的Ca(2+)内流，抑制海马锥体神经元中的NMDAR-mEPSC，改善大脑中动脉闭塞（MACO）大鼠的运动能力，减小局灶性脑缺血大鼠的梗死面积并降低中风死亡率。综上所述，我们的数据表明BQ-869的神经保护作用可能是通过抑制NMDA介导的兴奋性毒性实现的。这些发现表明BQ-869是最有效的NMDA受体拮抗剂，并为中风治疗提供了具有潜在治疗应用价值的新见解。
