Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins
Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins
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DOI：
10.1523/jneurosci.21-23-09334.2001
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发表时间：
2001-12-01
影响因子：
5.3
通讯作者：
Bregman, BS
中科院分区：
文献类型：
--
作者：
Coumans, JV;Lin, TTS;Bregman, BS
成年哺乳动物脊髓损伤后很少发生轴突再生。然而，通过改变神经元生长的内在能力或通过在损伤部位提供容许的环境，可以诱导成熟CNS轴突的再生长。胚胎脊髓移植和神经营养因子被用来影响成年大鼠脊髓完全横断后，在胸中部水平的轴突再生。在横断后立即（急性损伤）或延迟2-4周后（延迟或慢性移植）将移植物置于病变腔内，并通过植入的微型泵外源性给予载体或神经营养因子。在所有组中，宿主轴突都生长到移植物中。令人惊讶的是，当移植物和神经营养素延迟至横断后2-4周而不是急性应用时，脊髓上途径的再生和运动功能的恢复显著增加。只有在神经营养因子存在的情况下才能看到轴突生长回到病变下方的脊髓和移植物。此外，整个损伤部位的解剖连接的恢复与表现出足底放置和重量支撑的步进的动物的功能恢复相关。这些发现表明，脊髓损伤后进行干预的机会可能比最初设想的要大，并且长期损伤的CNS神经元可以重新启动生长，从而改善运动功能。
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.