National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, P. R. China.
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, P. R. China.
Sci Rep. 2017 Aug 30;7(1):10052. doi: 10.1038/s41598-017-10283-4.
Chronic cerebral hypoperfusion is a pathological state that is associated with the cognitive impairments in vascular dementia. Oxiracetam is a nootropic drug that is commonly used to treat cognitive deficits of cerebrovascular origins. However, oxiracetam is currently used as a racemic mixture whose effective ingredient has not been identified to date. In this study, we first identified that (S)-oxiracetam, but not (R)-oxiracetam, was the effective ingredient that alleviated the impairments of spatial learning and memory by ameliorating neuron damage and white matter lesions, increasing the cerebral blood flow, and inhibiting astrocyte activation in chronic cerebral hypoperfused rats. Furthermore, using MALDI-MSI and LC-MS/MS, we demonstrated that (S)-oxiracetam regulated ATP metabolism, glutamine-glutamate and anti-oxidants in the cortex region of hypoperfused rats. Altogether, our results strongly suggest that (S)-oxiracetam alone could be a nootropic drug for the treatment of cognitive impairments caused by cerebral hypoperfusion.
慢性脑灌注不足是一种与血管性痴呆认知障碍相关的病理状态。奥拉西坦是一种常用于治疗脑血管源性认知缺陷的益智药。然而，奥拉西坦目前被用作外消旋混合物，其有效成分迄今尚未确定。在这项研究中，我们首先确定（S）-奥拉西坦，而不是（R）-奥拉西坦，是通过改善神经元损伤和白质病变、增加脑血流量和抑制慢性脑灌注不足大鼠星形胶质细胞激活来缓解空间学习和记忆损伤的有效成分。此外，我们使用 MALDI-MSI 和 LC-MS/MS 表明，（S）-奥拉西坦调节了低灌注大鼠皮质区域的 ATP 代谢、谷氨酰胺-谷氨酸和抗氧化剂。总之，我们的研究结果强烈表明，（S）-奥拉西坦本身可能是一种治疗脑灌注不足引起的认知障碍的益智药。
