AUTHOR=Lu Haiyan , Song Xiaoyan , Wang Feng , Wang Guodong , Wu Yuncheng , Wang Qiaoshu , Wang Yongting , Yang Guo-Yuan , Zhang Zhijun TITLE=Hyperexpressed Netrin-1 Promoted Neural Stem Cells Migration in Mice after Focal Cerebral Ischemia JOURNAL=Frontiers in Cellular Neuroscience VOLUME=Volume 10 - 2016 YEAR=2016 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2016.00223 DOI=10.3389/fncel.2016.00223 ISSN=1662-5102 ABSTRACT=

Endogenous Netrin-1 (NT-1) protein was significantly increased after cerebral ischemia, which may participate in the repair after transient cerebral ischemic injury. In this work, we explored whether NT-1 can be steadily overexpressed by adeno-associated virus (AAV) and the exogenous NT-1 can promote neural stem cells migration from the subventricular zone (SVZ) region after cerebral ischemia. Adult CD-1 mice were injected stereotacticly with AAV carrying NT-1 gene (AAV-NT-1). Mice underwent 60 min of middle cerebral artery (MCA) occlusion 1 week after injection. We found that NT-1 mainly expressed in neuron and astrocyte, and the expression level of NT-1 significantly increased 1 week after AAV-NT-1 gene transfer and lasted for 28 days, even after transient middle cerebral artery occlusion (tMCAO) as well (p < 0.05). Immunohistochemistry results showed that the number of neural stem cells was greatly increased in the SVZ region of AAV-NT-1-transduced mice compared with control mice. Our study showed that overexpressed NT-1 promoted neural stem cells migration from SVZ. This result suggested that NT-1 is a promising factor for repairing and remodeling after focal cerebral ischemia.