Iarikov Dmitri E, Kim Byung G, Dai Hai-Ning, McAtee Marietta, Kuhn Penelope L, Bregman Barbara S
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.
J Neurotrauma. 2007 Apr;24(4):690-702. doi: 10.1089/neu.2006.0172.
Functional deficits following spinal cord injury (SCI) result from a disruption of corticofugal projections at the lesion site. Not only direct regeneration of the severed axons but also anatomical re-organization of spared corticofugal pathways can reestablish connections between the supraspinal and spinal motor centers. We have previously shown that delayed transplantation of fetal spinal cord tissue and neurotrophin administration by two weeks after SCI supported recovery of forelimb function in adult rats. The current study determined whether the same intervention enhances plasticity of corticofugal fibers at the midbrain and spinal cord level. Anterograde tracing of the left corticorubral fibers revealed that the animals with transplants and neurotrophins (BDNF or NT-3) increased the extent of the traced fibers crossing to the right red nucleus (RN), of which the axons are spared by a right cervical overhemisection lesion. More neurons in the left motor cortex were recruited by the treatment to establish connections with the right RN. The right corticorubral projections also increased the density of midline crossing fibers to the axotomized left RN in response to transplants and neurotrophins. Transplants plus NT-3, but not BDNF, significantly increased the amount of spared corticospinal fibers in the left dorsolateral funiculus at the spinal level both rostral and caudal to the lesion. These results suggest that corticofugal projections retain the capacity until at least two weeks after injury to undergo extensive reorganization along the entire neuraxis in response to transplants and neurotrophins. Targeting anatomical plasticity of corticofugal projections may be a promising strategy to enhance functional recovery following incomplete SCI.
脊髓损伤（SCI）后的功能缺陷是由损伤部位的皮质下行投射中断所致。不仅切断的轴突直接再生，而且未受损的皮质下行通路的解剖重组也可重新建立脊髓上运动中枢与脊髓运动中枢之间的联系。我们之前已经表明，成年大鼠脊髓损伤两周后延迟移植胎儿脊髓组织并给予神经营养因子可促进前肢功能恢复。本研究确定相同的干预措施是否能增强中脑和脊髓水平皮质下行纤维的可塑性。对左侧皮质红核纤维进行顺行示踪显示，接受移植和神经营养因子（脑源性神经营因子或神经营养因子-3）治疗的动物，其示踪纤维交叉至右侧红核（RN）的范围增加，右侧颈髓半横断损伤使其轴突得以保留。治疗可使左侧运动皮层中更多的神经元被募集来与右侧红核建立联系。右侧皮质红核投射也因移植和神经营养因子而增加了向轴突切断的左侧红核的中线交叉纤维密度。移植加神经营养因子-3而非脑源性神经营因子，显著增加了损伤部位头端和尾端脊髓水平左侧背外侧索中保留的皮质脊髓纤维数量。这些结果表明，皮质下行投射在损伤后至少两周内仍保留着响应移植和神经营养因子而沿整个神经轴进行广泛重组的能力。针对皮质下行投射的解剖可塑性可能是促进不完全性脊髓损伤后功能恢复的一种有前景的策略。
