Coumans J V, Lin T T, Dai H N, MacArthur L, McAtee M, Nash C, Bregman B S
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.
J Neurosci. 2001 Dec 1;21(23):9334-44. doi: 10.1523/JNEUROSCI.21-23-09334.2001.
Little axonal regeneration occurs after spinal cord injury in adult mammals. Regrowth of mature CNS axons can be induced, however, by altering the intrinsic capacity of the neurons for growth or by providing a permissive environment at the injury site. Fetal spinal cord transplants and neurotrophins were used to influence axonal regeneration in the adult rat after complete spinal cord transection at a midthoracic level. Transplants were placed into the lesion cavity either immediately after transection (acute injury) or after a 2-4 week delay (delayed or chronic transplants), and either vehicle or neurotrophic factors were administered exogenously via an implanted minipump. Host axons grew into the transplant in all groups. Surprisingly, regeneration from supraspinal pathways and recovery of motor function were dramatically increased when transplants and neurotrophins were delayed until 2-4 weeks after transection rather than applied acutely. Axonal growth back into the spinal cord below the lesion and transplants was seen only in the presence of neurotrophic factors. Furthermore, the restoration of anatomical connections across the injury site was associated with recovery of function with animals exhibiting plantar foot placement and weight-supported stepping. These findings suggest that the opportunity for intervention after spinal cord injury may be greater than originally envisioned and that CNS neurons with long-standing injuries can reinitiate growth, leading to improvement in motor function.
成年哺乳动物脊髓损伤后轴突再生很少发生。然而，通过改变神经元的内在生长能力或在损伤部位提供适宜的环境，可以诱导成熟中枢神经系统轴突的生长。在成年大鼠胸段中部完全脊髓横断后，使用胎儿脊髓移植和神经营养因子来影响轴突再生。移植在横断后立即（急性损伤）或延迟2 - 4周后（延迟或慢性移植）植入损伤腔，并且通过植入的微型泵外源性给予载体或神经营养因子。所有组中的宿主轴突都长入了移植组织。令人惊讶的是，当移植和神经营养因子延迟至横断后2 - 4周而不是急性应用时，脊髓上通路的再生和运动功能的恢复显著增加。只有在存在神经营养因子时，才可见轴突长回到损伤部位下方的脊髓和移植组织中。此外，损伤部位解剖连接的恢复与功能恢复相关，动物表现出足底放置和负重行走。这些发现表明脊髓损伤后干预的机会可能比最初设想的更大，并且长期损伤的中枢神经系统神经元可以重新启动生长，从而导致运动功能改善。
