Neuroscience and Neuroengineering Research Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
Front Med. 2011 Mar;5(1):86-93. doi: 10.1007/s11684-011-0118-x. Epub 2011 Mar 17.
Netrin-1 (NT-1) is one of the axon-guiding molecules that are critical for neuronal development. Because of its structural homology to the endothelial mitogens, NT-1 may have similar effects on vascular network formation. NT-1 was shown to be able to stimulate the proliferation and migration of human cerebral endothelial cells in vitro and also promote focal neovascularization in adult brain in vivo. In the present study, we reported the delivery of NT-1 using an adeno-associated virus (AAV) vector (AAV-NT-1) into mouse brain followed by transient middle cerebral artery occlusion (tMCAO). We found that AAV vectors did not elicit a detectable inflammatory response, cell loss or neuronal damage after brain transduction. The level of NT-1 was increased in the AAV-NT-1-transduced tMCAO mice compared with the control mice. Furthermore, the neurobehavioral outcomes were significantly improved in AAV-NT-1-transduced mice compared with the control animals (P<0.05) 7 days after tMCAO. Our data suggests that NT-1 plays a neuronal function recovery role in ischemic brain and that NT-1 gene transfer might present a valuable approach to treat brain ischemic disorders.
神经导向因子 1（NT-1）是对神经元发育至关重要的轴突导向分子之一。由于其结构与内皮细胞有丝分裂原同源，NT-1 可能对血管网络形成有类似的影响。NT-1 被证明能够在体外刺激人脑血管内皮细胞的增殖和迁移，并且在体内也能促进成年大脑的局灶性新血管形成。在本研究中，我们报告了使用腺相关病毒（AAV）载体（AAV-NT-1）将 NT-1 递送到小鼠大脑中，随后进行短暂性大脑中动脉闭塞（tMCAO）。我们发现，AAV 载体在脑转导后不会引起可检测到的炎症反应、细胞丢失或神经元损伤。与对照组相比，在 AAV-NT-1 转导的 tMCAO 小鼠中，NT-1 的水平增加。此外，与对照组动物相比，在 tMCAO 后 7 天，AAV-NT-1 转导的小鼠的神经行为结果显著改善（P<0.05）。我们的数据表明，NT-1 在缺血性大脑中发挥神经元功能恢复作用，NT-1 基因转移可能为治疗脑缺血性疾病提供一种有价值的方法。
