Yu Panpan, Huang Lidong, Zou Jian, Yu Zhihua, Wang Yanxia, Wang Xiaofei, Xu Liang, Liu Xinqiu, Xu Xiao-Ming, Lu Pei-Hua
Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Neurobiol Dis. 2008 Dec;32(3):535-42. doi: 10.1016/j.nbd.2008.09.012. Epub 2008 Sep 30.
Nogo-66 receptor (NgR), a common receptor for the three known myelin-associated inhibitors, i.e., Nogo-A, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp), plays a key role in the failure of axonal regeneration in the adult mammalian central nervous system (CNS). Here we report a novel vaccine approach that stimulates the production of anti-NgR antibody to overcome NgR-mediated growth inhibition after spinal cord injury (SCI). We showed that adult rats immunized with recombinant NgR produced high titers of the anti-NgR antibody and that antisera obtained from the immunized rats promoted neurite outgrowth of rat cerebellar neurons on the inhibitory MAG substrate in vitro. In a spinal cord dorsal hemisection model, NgR immunization promoted regeneration of lesioned corticospinal tract (CST) axons, anterogradely labeled with biotin dextran amine (BDA), beyond the lesion site. In a contusive SCI model, NgR immunization markedly reduced the total lesion volume and improved Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and grid walking performance. Thus, the NgR vaccine approach may represent a promising repair strategy to promote structural and functional recovery following SCI.
Nogo-66受体（NgR）是三种已知的髓磷脂相关抑制因子，即Nogo-A、髓磷脂相关糖蛋白（MAG）和少突胶质细胞髓磷脂糖蛋白（OMgp）的共同受体，在成年哺乳动物中枢神经系统（CNS）轴突再生失败中起关键作用。在此，我们报告一种新型疫苗方法，该方法可刺激抗NgR抗体的产生，以克服脊髓损伤（SCI）后NgR介导的生长抑制。我们发现，用重组NgR免疫的成年大鼠产生了高滴度的抗NgR抗体，并且从免疫大鼠获得的抗血清在体外促进了大鼠小脑神经元在抑制性MAG底物上的神经突生长。在脊髓背侧半切模型中，NgR免疫促进了用生物素葡聚糖胺（BDA）顺行标记的损伤皮质脊髓束（CST）轴突再生至损伤部位以外。在挫伤性SCI模型中，NgR免疫显著减小了总损伤体积，并改善了Basso、Beattie和Bresnahan（BBB）运动评分量表及网格行走性能。因此，NgR疫苗方法可能是一种有前景的促进SCI后结构和功能恢复的修复策略。
