Ye J H, Houle J D
Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Exp Neurol. 1997 Jan;143(1):70-81. doi: 10.1006/exnr.1996.6353.
Axonal regeneration has been demonstrated by supraspinal neurons long after a spinal cord injury, although this potential seems limited to a few neurons in specific nuclear groups. Whether the regenerative response could be enhanced by exposure to neurotrophic factors was examined in this study. Neurons injured during a cervical spinal cord hemisection lesion were labeled with true blue (TB). Four weeks after spinal cord injury, gel foam saturated with brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), ciliary neurotrophic factor (CNTF), or saline as a control was placed into the lesion cavity. The gel foam was replaced with fresh factor after 3 days, and 4 days later a peripheral nerve (PN) graft was apposed to the rostral cavity wall. Four weeks later neurons that grew an axon into the PN graft were labeled with nuclear yellow (NY). Cells that were double labeled (TB and NY) represented chronically injured neurons capable of axon regeneration. Cells labeled with NY only were either acutely injured neurons capable of axonal regrowth or uninjured neurons that had sprouted into the PN graft. The total number of TB/NY-labeled neurons was significantly increased following exposure to BDNF, NT-3, or CNTF. Specific regions most influenced by NT-3 and BDNF were the reticular formation and red nucleus. Treatment with CNTF resulted in a significant increase in most brain regions with a major contribution to descending pathways in the spinal cord, the motor cortex being the exception, with no evidence of axonal regeneration by neurons forming the corticospinal tract. The total number of NY-only labeled neurons also was significantly greater after treatment with BDNF or CNTF. These results demonstrate the potential to increase the regenerative response of specific chronically injured supraspinal neurons by application of neurotrophic factors to the injury site.
脊髓损伤后很长时间，脊髓上神经元已被证明具有轴突再生能力，尽管这种潜力似乎仅限于特定核团中的少数神经元。本研究探讨了暴露于神经营养因子是否能增强再生反应。在颈髓半切损伤中受损的神经元用真蓝（TB）标记。脊髓损伤四周后，将浸有脑源性神经营养因子（BDNF）、神经营养素3（NT-3）、睫状神经营养因子（CNTF）的明胶海绵或作为对照的生理盐水置于损伤腔内。3天后更换为新鲜因子，4天后将周围神经（PN）移植物贴附于头端腔壁。四周后，将轴突生长到PN移植物中的神经元用核黄（NY）标记。双重标记（TB和NY）的细胞代表能够轴突再生的慢性损伤神经元。仅用NY标记的细胞要么是能够轴突再生的急性损伤神经元，要么是已长入PN移植物的未损伤神经元。暴露于BDNF、NT-3或CNTF后，TB/NY标记神经元的总数显著增加。受NT-3和BDNF影响最大的特定区域是网状结构和红核。用CNTF治疗导致大多数脑区显著增加，对脊髓下行通路有主要贡献，运动皮层除外，形成皮质脊髓束的神经元没有轴突再生的证据。用BDNF或CNTF治疗后，仅用NY标记的神经元总数也显著增加。这些结果表明，通过将神经营养因子应用于损伤部位，有可能增强特定慢性损伤脊髓上神经元的再生反应。
