Netrin-1 hyper-expression of in the brain promotes angiogenesis and improves neurological outcome in transient MCAO mice

作     者：Hai-Yan LU~1,Yong-Ting WANG~2,Xiao-Song HE~2,Fa-Lei YUAN~2,Xiao-Jie LING~2,Bo-Hua XIE~2,Guang-Hui TANG~2, Jun HUANG~2,Yao-Hui TANG~2,Sheng-Di CHEN~1,Guo-Yuan YANG~(1,2,*) 1 Departments of Neurology,Ruijin Hospital,Shanghai JiaoTong University School of Medicine,Shanghai 200025, China 2 Neuroscience and Neuroengineering Research Center,Med-X Research Institute,Shanghai Jiao Tong University, Shanghai 200030,China 

会议名称：《中国神经科学学会第九届全国学术会议暨第五次会员代表大会》

会议日期：2011年

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

关 键 词：adeno-associated virus angiogenesis gene transfer ischemia middle cerebral artery occlusion netrin-1 

摘      要：正Objective Netrin-1（NT-1） is one of the axon-guiding molecules that are critical for neuronal ***-1 stimulates proliferation and migration of human cerebral endothelial cells in vitro and promotes focal neovascularization in adult brain in *** is unknown whether NT-1 improves long-term functional outcome after ischemic *** aim of this study is to determine whether hyper-expression of NT-1 through adenoassociated virus（AAV） -mediated gene transfer enhances neurovascular remodeling and improves functional outcome in mouse model of focal cerebral *** AAV-NT-1 virus was stereotactic injected into the basal ganglia of male CD-1 mice（n=30）.Seven days after injection,these mice underwent 60 minutes of transient middle cerebral artery occlusion（tMCAO） followed by 1 to 4 weeks of *** of NT-1 and its receptors was quantified by Western blot and *** volume and behavioral analyses were performed after tMCAO. Synchronic radiation angiography was used to detect the changes of cerebral *** NT-1 expression in the ischemic hemisphere was enhanced after AAV-NT-1 gene *** neurons and astrocytes but not endothelial cells expressed ***-1 receptors（DCC and UNC5H2） also expressed in neurons and ***-expression of NT-1 decreased infarct volume in the AAV-NT-1-transduced mice compared to the control（P0.01）.Long-term observation demonstrated that neurobehavioral outcomes were greatly improved in the AAV-NT-1-tranduced mice compared to the control（P0.05）.Further study demonstrated that the microvessel counts were significantly increased in the AAV-NT-1 transduced mice（P0.05）.Synchrotron radiation angiography showed that the brunches of MCA was increased in NT-1 treated *** Our data demonstrate that NT-1 hyper-expression reduced ischemic injury and promoted functional *** may due to enhancement of focal neovascularization.