Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan; Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, PR China.
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Pharmacol Biochem Behav. 2020 Apr;191:172904. doi: 10.1016/j.pbb.2020.172904. Epub 2020 Mar 7.
Although stroke is the most common acute cerebrovascular disease, there are no currently effective therapeutic drugs for ischemic stroke. (R,S)-ketamine has been shown to protect against brain injury in rodents after middle cerebral artery occlusion (MCAO). Interestingly, we reported that (R)-ketamine has greater beneficial effects than (S)-ketamine in animal models of depression and Parkinson's disease. This study was undertaken whether two enantiomers of ketamine show neuroprotective effects in MCAO model. MCAO-induced brain injury and behavioral abnormalities in mice was attenuated by subsequent administration of (R)-ketamine (10 mg/kg, twice, 1 and 24 h after MCAO), but not (S)-ketamine (10 mg/kg, twice, 1 and 24 h after MCAO). Furthermore, the treatment with (R)-ketamine (10 mg/kg, twice, 30 min before and 24 h after MCAO) significantly protected against brain injury and behavioral abnormalities in mice after MCAO. These findings suggest that (R)-ketamine can protect against neuronal injury and behavioral abnormalities in mice after MCAO. Therefore, it is likely that (R)-ketamine could represent a therapeutic drug for ischemic stroke.
尽管中风是最常见的急性脑血管疾病，但目前尚无治疗缺血性中风的有效药物。（R，S）-氯胺酮已被证明可在大脑中动脉闭塞（MCAO）后保护啮齿动物的脑损伤。有趣的是，我们报告说（R）-氯胺酮在抑郁症和帕金森病的动物模型中比（S）-氯胺酮具有更大的有益作用。本研究旨在探讨氯胺酮的两种对映异构体在 MCAO 模型中是否具有神经保护作用。（R）-氯胺酮（MCAO 后 1 和 24 小时，10mg/kg，两次）可减轻 MCAO 诱导的小鼠脑损伤和行为异常，但（S）-氯胺酮（10mg/kg，两次）则不能。此外，（R）-氯胺酮（MCAO 前 30 分钟和 MCAO 后 24 小时，10mg/kg，两次）的治疗可显著减轻 MCAO 后小鼠的脑损伤和行为异常。这些发现表明（R）-氯胺酮可保护 MCAO 后小鼠的神经元损伤和行为异常。因此，（R）-氯胺酮可能代表治疗缺血性中风的一种治疗药物。
