Quintard H, Lorivel T, Gandin C, Lazdunski M, Heurteaux C
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France; Centre Hospitalo-Universitaire de Nice, Hôpital St Roch, 4 rue Pierre Dévoluy, 06000 Nice, France.
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France.
Neuroscience. 2014 Sep 26;277:72-86. doi: 10.1016/j.neuroscience.2014.06.047. Epub 2014 Jun 30.
Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. NeuroAid (MLC601 and MLC901), a Traditional Medicine used in China for patients after stroke has been previously reported to induce neuroprotection and neuroplasticity. This study was designed to evaluate the neuroprotective and neuroregenerative effects of MLC901 in a rat model of TBI. TBI was induced by a moderate lateral fluid percussion applied to the right parietal cortex. MLC901 was injected intraperitoneally at 2h post-TBI, and then administered in drinking water at a concentration of 10mg/ml until sacrifice of the animals. The cognitive deficits induced by TBI were followed by using the "what-where-when" task, which allows the measurement of episodic-like memory. MLC901 treatment decreased brain lesions induced by TBI. It prevented the serum increase of S-100 beta (S100B) and neuron-specific enolase (NSE), which may be markers to predict the neurologic outcome in human patients with TBI. MLC901 reduced the infarct volume when injected up to 2h post-TBI, prevented edema formation and assisted its resolution, probably via the regulation of aquaporin 4. These positive MLC901 effects were associated with an upregulation of vascular endothelial growth factor (VEGF) as well as an increase of endogenous hippocampal neurogenesis and gliogenesis around the lesion. Furthermore, MLC901 reduced cognitive deficits induced by TBI. Rats subjected to TBI displayed a suppression of temporal order memory, which was restored by MLC901. This work provides evidence that MLC901 has neuroprotective and neurorestorative actions, which lead to an improvement in the recovery of cognitive functions in a model of traumatic brain injury.
创伤性脑损伤(TBI)是一种常见且临床异质性很高的神经系统疾病,会造成巨大的社会经济后果。NeuroAid(MLC601和MLC901)是中国用于中风后患者的一种传统药物,此前有报道称其具有神经保护和神经可塑性作用。本研究旨在评估MLC901在TBI大鼠模型中的神经保护和神经再生作用。通过对右侧顶叶皮质施加中度侧方液体冲击诱导TBI。在TBI后2小时腹腔注射MLC901,然后以10mg/ml的浓度加入饮用水中给药,直至处死动物。使用“什么-哪里-何时”任务跟踪TBI诱导的认知缺陷,该任务可测量情景样记忆。MLC901治疗减少了TBI诱导的脑损伤。它阻止了血清中S-100β(S100B)和神经元特异性烯醇化酶(NSE)的升高,这可能是预测人类TBI患者神经学结果的标志物。在TBI后2小时内注射MLC901可减少梗死体积,防止水肿形成并促进其消退,可能是通过调节水通道蛋白4实现的。MLC901的这些积极作用与血管内皮生长因子(VEGF)的上调以及损伤周围内源性海马神经发生和神经胶质生成的增加有关。此外,MLC901减少了TBI诱导的认知缺陷。遭受TBI的大鼠表现出时间顺序记忆的抑制,而MLC901可使其恢复。这项工作提供了证据,证明MLC901具有神经保护和神经修复作用,可改善创伤性脑损伤模型中认知功能的恢复。