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Expression of netrin-1 and its receptors, deleted in colorectal cancer and uncoordinated locomotion-5 homolog B, in rat brain following focal cerebral ischemia reperfusion injury

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Neural Regeneration Research 2013年第1期8卷 64-69页

作者： Xiaodan Wang Jinming Xu Jieqin Gong Hui Shen Xiaoping Wang Department of Neurology Shanghai First People's Hospital Shanghai Jiao Tong University School of Medicine Department of Neurology Suzhou Kowloon Hospital Shanghai Jiao Tong University School of Medicine

Netrin-1 is currently one of the most highly studied axon guidance factors. Netrin-1 is widely expressed in the embryonic central nervous system, and together with the deleted in colorectal cancer and uncoordinated locomotion-5 homolog B receptors, netrin-1 plays a guiding role in the construction of neural conduction pathways and the directional migration of neuronal cells. In this study, we established a rat middle cerebral artery ischemia reperfusion model using the intraluminal thread technique. Immunofluorescence microscopy showed that the expression of netrin-1 and deleted in colorectal cancer in the ischemic penumbra was upregulated at 1 day after reperfusion, reached a peak at 14 days, and decreased at 21 days. There was no obvious change in the expression of uncoordinated locomotion-5 homolog B during this time period. Double immunofluorescence labeling revealed that netrin-1 was expressed in neuronal cells and around small vessels, but not in astrocytes and microglia, while deleted in colorectal cancer was localized in the cell membranes and protrusions of neurons and astrocytes. Our experimental findings indicate that netrin-1 may be involved in post-ischemic repair and neuronal protection via deleted in colorectal cancer receptors.

关键词： neural regeneration brain injury cerebral ischemia and reperfusion netrin-1 uncoordinatedlocomotion-5 homolog B deleted in colorectal cancer neuron brain injury grant-supported paper photographs-containing paper neuroregeneration

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Netrin-1 overexpression in bone marrow mesenchymal stem cells promotes functional recovery in a rat model of peripheral nerve injury

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The Journal of Biomedical Research 2015年第5期29卷 380-389页

作者： Xianjin Ke Qian Li Li Xu Ying Zhang Dongmei Li Jianhua Ma Xiaoming Mao Department of Neurology Affiliated Hospital of Jiangsu University Department of Endocrinology Nanjing First HospitalNanjing Medical University

Transplantation of bone marrow mesenchymal stem cells （BMSCs） has been developed as a new method of treat- ing diseases of the peripheral nervous system. While netrin-1 is a critical molecule for axonal path finding and nerve growth, it may also affect vascular network formation. Here, we investigated the effect of transplanting BMSCs that produce netrin-1 in a rat model of sciatic nerve crush injury. We introduced a sciatic nerve crush injury, and then injected 1×10^6 BMSCs infected by a recombinant adenovirus expressing netrin-1 Ad5-Netrin-l-EGFP or culture medium into the injured part in the next day. At day 7, 14 and 28 after injection, we measured motor nerve con- duction and detected mRNA expressions of netrin-1 receptors UNC5B and deleted in colorectal cancer （DCC）, and neurotrophic factors brain-derived neurotrophic factor （BDNF） and nerve growth factor （NGF） by real-time PCR. We also detected protein expressions of BDNF and NGF by Western blotting assays and examined BMSCs that incorporated into myelin and vascellum. The results showed that BMSCs infected by AdS-Netrin- 1-EGFP significantly improved the function of the sciatic nerve, and led to increased expression of BDNF and NGF （P〈0.05）. Moreover, 28 days after injury, more Schwann cells were found in BMSCs infected by AdS- Netrin-l-EGFP compared to control BMSCs. In conclusion, transplantation of BMSCs that produce netrin-1 improved the function of the sciatic nerve after injury. This method may be a new treatment of nerve injury.

关键词： bone marrow mesenchymal stem cells netrin-1 UNCSB deleted in colorectal cancer brain-derivedneurotrophic factor nerve growth factor

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