MRI 引导的聚焦超声联合微泡靶向移植BDNF基因转染的神经干细胞治疗阿尔茨海默病的研究

项目名称： MRI 引导的聚焦超声联合微泡靶向移植BDNF基因转染的神经干细胞治疗阿尔茨海默病的研究

项目编号： No.U1204810

项目类型： 联合基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 王峰

作者单位： 新乡医学院

项目金额： 30万元

中文摘要： 阿尔茨海默病( AD)是一种神经退行性疾病,严重影响了患者的健康和生存能力。研究表明，移植外源性神经干细胞（NSC）能够补充替代AD患者脑内退变的神经元，而脑源性神经生长因子（BDNF）也是AD治疗有效的靶点。所以如果用BDNF基因转染NSC将能增强其治疗AD的效果。由于血脑屏障（BBB）的存在，阻碍NSC向脑内移植，影响AD的治疗效果。因低频聚焦超声联合微泡能够无创开放BBB，促进大分子物质进入脑内，所以本课题拟采用MRI 实时引导聚焦超声联合微泡辐照大鼠海马开放BBB，促进编码BDNF基因的逆转录病毒转染的大鼠NSC通过BBB，靶向移植入海马，观察其对AD大鼠行为及组织结构的影响，探讨BDNF基因治疗与NSC移植结合对AD影响的作用效果及机理。通过以上技术，无创、可逆开放BBB ，将进一步增加BDNF基因转染的NSC在治疗脑疾病方面的优势，为AD的治疗开辟了新的途径。

中文关键词： 阿尔茨海默病；血脑屏障；神经干细胞；聚焦超声；脑源性神经生长因子

英文摘要： Alzheimer’s Disease is one of the most serious of a chronic and progressive neurodegenerative disease, which disturbs seriously the health and survival ability of patients. Studies have shown that the transplantation of endogenous neural stem cells (NSC) could treat the neuron degeneration of the brain of AD patients.The brain-derived neurotrophic factor (BDNF) can regulate synaptic plasticity in the hippocampus and forebrain cholinergic nervous system, and affect learning and memory, which Will be conducive to the treatment of AD. So BDNF will become the treament target of AD. BDNF gene transfected NSC will be able to enhance the effect of the treatment of AD. Because NSC delivery to the central nervous system are easily blocked by the BBB, the treatment of AD will be invalid. The method of ultrasound combined with ultrasound contrast agents can open BBB Safely , reversiblely and locally. In our study, MRI-guided focused ultrasound combined with microbubble was used to radiate the hippocampus for opening BBB locally, which to promote NSC transfeced by retrovirus encoding BDNF gene (NSC/BNDF) to go through BBB. The behavioral test and histological examination were used to evaluate the effect of NSC/BNDF on AD model rats. Through studying the technique of ultrasound combined with microbubble for BBB opening, wh

英文关键词： Alzheimer's disease；Blood-brain barrier；Neural stem cells；Focused ultrasound;；BDNF