脑缺血(脑梗塞)是由于脑动脉狭窄加重或完全闭塞,导致脑组织缺血、缺氧、坏死,从而引起神经功能障碍的一种脑血管病。脑缺血是很常见的中枢神经损伤,其主要致病因素有:高血压病、冠心病、糖尿病等,多见于45~70岁中老年人。生存下来的脑缺血损伤病人大都会有后遗症,影响正常生活,严重的脑缺血病人生活不能自理甚至危及生命安全。中枢神经再生是再生医学的研究热点之一。
中国科学院遗传与发育生物学研究所戴建武研究员领导的再生医学实验室将脑缺血部位富含的层粘连蛋白作为脑缺血损伤治疗的靶点,研制出了能特异结合层粘连蛋白的脑神经营养因子(LBD-BDNF),并与第三军医大附属重庆西南医院神经外科合作,用动物模型验证了LBD-BDNF可以有效促进脑缺血损伤后的恢复。
他们制备了大鼠大脑中动脉堵塞的脑缺血模型,证明了LBD-BDNF可以特异地结合于脑缺血部位,显著减少急性期内半暗区神经元凋亡和坏死;一周后,LBD-BDNF治疗组脑缺血大脑半球的梗塞面积显著减少;四周后,海马区域神经发生明显增强,神经行为能力明显恢复。这一系列结果表明:LBD-BDNF可以通过结合于脑缺血部位的层粘连蛋白来发挥其定向的神经营养作用,促进脑缺血损伤的恢复。
这项工作是对脑缺血损伤治疗方法的新探索,为缺血损伤后神经再生提供了新思路。该治疗思路也可用于探索对帕金森氏症等神经退行性疾病的治疗。
这项工作以戴建武实验室博士研究生韩倩倩和重庆西南医院神经外科博士研究生李博为共同第一作者,发表在《生物材料》(Biomaterials)上(Doi:10.1016/j.biomaterials.2011.03.072)。(生物谷Bioon.com)
生物谷推荐原文出处:
Biomaterials DOI: 10.1016/j.biomaterials.2011.03.072
The promotion of cerebral ischemia recovery in rats by laminin-binding BDNF
Qianqian Han, Bo Li, Hua Feng, Zhifeng Xiao, Bing Chen, Yannan Zhao, Jingchun Huang and Jianwu Dai
Brain-derived neurotrophic factor (BDNF) has been shown to have therapeutic effects on cerebral ischemia. However, the delivery approach limits its application. Laminin is a rich extra cellular matrix in the central nervous system, and is highly expressed in the ischemic region after cerebral ischemia. We reported here by fusing with laminin-binding domain (LBD) to BDNF to construct laminin-binding BDNF (LBD-BDNF). LBD-BDNF could target accumulated laminin in the ischemic region and exert targeting therapy of injured neurons after ischemia. We examined the laminin-binding ability and neurotrophic bioactivity of LBD-BDNF in vitro, and assessed its targeting therapy using a rat permanent middle cerebral artery occlusion (MCAO) model in vivo. It was found that LBD-BDNF could specifically bind to laminin and maintain BDNF activity both in vitro and in vivo. LBD-BDNF treatment attenuated neural-degeneration after MCAO, and also resulted in a reduction of infarct volume that is associated with a parallel improvement in neurological functional outcome and neurogenesis in the dentate gyrus of hippocamp.