An adenovirus vector for neurotrophin transfection induces compressed spinal cord of adults rat

我们研究了腺病毒载体(AxCAhGDNF)编码的胶质细胞源性神经营养因子(GDNF)对损伤脊髓损伤的神经保护作用。采用硬膜外静重加压的方法造成大鼠胸段脊髓损伤。将腺病毒载体直接注射入胸段脊髓后，进行组织学、免疫组织化学和免疫印迹分析。AxCAlacZ致伤后1周，损伤处和注射部位均可见β-半乳糖苷酶活性的表达，注射后4~6周仍有表达。损伤后注射AxCAhGDNF的大鼠脊髓运动神经元、反应性星形胶质细胞和少突胶质细胞中GDNF有较强的免疫标记，病毒诱导的人GDNF在脊髓组织中有转录。尼氏染色细胞计数显示，注射AxCAhGDNF可显著防止损伤后2~4周脊髓运动神经元的丢失。这些结果表明，腺病毒介导的GDNF基因转移可以预防成年人脊髓损伤后运动神经元的变性。

We investigated neurotrotective effect of glial cell lined-derived neurotrophic factor (GDNF) encoded by an adenovirus vector (AxCAhGDNF) on the injured spinal cord lesions. The rat thoracic spinal cord was experimentally injured by extradural static weight compression. After the direct injection of the adenovirus vector into thoracic spinal cord, histological and immunohistochemical analysis and immunoblot analysis were examined. One week after the injury with AxCAlacZ, the animals showed expression of β-galactosidase activity in injured and injected lesions and the expression was visualized until 4-6 weeks after injection. Animals injured and injected with AxCAhGDNF showed intense immunolabeling for GDNF in lesioned spinal cord motoneurons, reactive astrocyte and oligodendrocyte, and expression of virus induced human GDNF mRNA transcripts in the spinal cord tissue. Nissl-stained cell counts revealed that the injection with AxCAhGDNF significantly prevented the loss of lesioned spinal cord motoneurons 2-4 weeks after injury. These results indicate that the adenovirus-mediated gene transfer of GDNF may prevent the degeneration of motoneurons in adult humans with spinal cord injury.