Kilic Ertugrul, Kilic Ulkan, Bacigaluppi Marco, Guo Zeyun, Abdallah Nada Ben, Wolfer David P, Reiter Russel J, Hermann Dirk M, Bassetti Claudio L
Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
J Pineal Res. 2008 Sep;45(2):142-8. doi: 10.1111/j.1600-079X.2008.00568.x. Epub 2008 Feb 14.
Melatonin is a potent antioxidant with neuroprotective activity in animal models of ischemic stroke, which based on its lack of serious toxicity has raised hopes that it might be used for human stroke treatment in the future. This study investigated how subacute delivery of melatonin, starting at 24 hr after stroke onset, and continuing for 29 days (4 mg/kg/day; via drinking water), influences neuronal survival, endogenous neurogenesis, motor recovery and locomotor activity in C57Bl6/j mice submitted to 30-min middle cerebral artery occlusion. Histologic studies showed that melatonin improved neuronal survival and enhanced neurogenesis, even when applied 1 day after stroke. Cell survival was associated with a long-lasting improvement of motor and coordination deficits, evaluated by the grip strength and RotaRod tests, as well as with attenuation of hyperactivity and anxiety of the animals as revealed in open field tests. The robust functional neurologic improvements encourage proof-of-concept studies with melatonin in human stroke patients.
褪黑素是一种在缺血性中风动物模型中具有神经保护活性的强效抗氧化剂，基于其无严重毒性，人们寄希望于未来可将其用于人类中风治疗。本研究调查了中风发作后24小时开始、持续29天（4毫克/千克/天；通过饮水给药）的亚急性褪黑素给药如何影响接受30分钟大脑中动脉闭塞的C57Bl6/j小鼠的神经元存活、内源性神经发生、运动恢复和运动活动。组织学研究表明，即使在中风后1天应用褪黑素，也能改善神经元存活并增强神经发生。通过握力和转棒试验评估，细胞存活与运动和协调缺陷的长期改善相关，同时也与旷场试验中显示的动物多动和焦虑减轻相关。褪黑素在功能神经学方面的显著改善鼓励了针对人类中风患者开展褪黑素的概念验证研究。
