DNA vaccine against NgR promotes functional recovery after spinal cord injury in adult rats
DNA vaccine against NgR promotes functional recovery after spinal cord injury in adult rats
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DOI：
10.1016/j.brainres.2007.02.013
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发表时间：
2007-05
期刊：
影响因子：
2.9
通讯作者：
Pan-pan Yu;Lidong Huang;Jian Zou;Huiqing Zhu;Xiao-fei Wang;Zhihua Yu;Xiao-Ming Xu;P. Lu
中科院分区：
文献类型：
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作者：
Pan-pan Yu;Lidong Huang;Jian Zou;Huiqing Zhu;Xiao-fei Wang;Zhihua Yu;Xiao-Ming Xu;P. Lu
NgR是三种髓磷脂相关抑制剂的共同受体，并介导它们对神经突生长的抑制活性。在本研究中，我们研究了一种靶向NgR的DNA疫苗是否能在促进脊髓损伤（SCI）恢复中发挥有益作用。我们成功构建了抗NgR的DNA疫苗，并在体外和体内高效表达。抗ngr DNA疫苗免疫大鼠后，可诱导低水平的抗体应答和T细胞介导的免疫应答。从抗ngr DNA接种大鼠提取的抗血清可以部分逆转MAG对神经突生长的抑制作用。当大鼠遭受挫伤性脊髓损伤时，接种疫苗的大鼠表现出比对照组更好的功能恢复。在那些接种疫苗的大鼠中，诱导T细胞反应并产生针对NgR的抗体，功能改善甚至更好。三维重建的组织学评估进一步表明，与对照组相比，接种疫苗的大鼠病变总体积减少了30.8%。这些结果共同表明，抗NgR的DNA疫苗可以显著改善挫伤性脊髓损伤大鼠的功能恢复，并且疫苗接种方法可能为促进脊髓损伤修复提供了一种有希望的策略。
NgR is a common receptor for three myelin-associated inhibitors and mediates their inhibitory activities on neurite outgrowth. In the present study, we investigated whether a DNA vaccine targeting NgR could play a beneficial role in improving recovery from spinal cord injury (SCI). We demonstrated that a DNA vaccine against NgR was successfully constructed and expressed efficiently in vitro and in vivo. After immunization with anti-NgR DNA vaccine, a low level of antibody response and a T cell-mediated immune response were induced in the vaccinated rats. And the antisera taken from the anti-NgR DNA vaccinated rats could partly reverse the inhibition of MAG on neurite outgrowth. When the rats were subjected to a contusive SCI, the vaccinated rats showed much better functional recovery than the controls. In those vaccinated rats that induced a T cell response and generated antibodies against NgR, functional improvements were even better. Histological assessments by three-dimensional reconstruction further demonstrated that the total lesion volume in the vaccinated rats was reduced by 30.8% compared to the controls. These results collectively suggest that DNA vaccine against NgR can significantly improve functional recovery in rats that received contusive SCI and that the vaccination approach may provide a promising strategy for promoting SCI repair.