Rasouli Alexandre, Bhatia Nitin, Suryadevara Sourabh, Cahill Kim, Gupta Ranjan
University of California, Irvine, 2226 Gillespie Neuroscience Research Facility, Irvine, CA 92697, USA.
J Bone Joint Surg Am. 2006 Nov;88(11):2400-10. doi: 10.2106/JBJS.E.01424.
Recovery after injury to the peripheral nervous system is based on the pro-regenerative relationship between axons and the extracellular matrix, a relationship established by Schwann cells. As mechanical conditioning of Schwann cells has been shown to stimulate their regenerative behavior, we sought to determine whether transplantation of these cells to the central nervous system (i.e., the spinal cord), with its limited regenerative capacity after injury, would improve axonal regeneration and functional recovery.
A moderate contusion injury of the spinal cord was created with a force-directed impactor in forty-eight adult Sprague-Dawley rats, and, at one week postinjury, the spinal cords were reexposed in all animals. In twenty-four of these animals, peripheral nerve grafts with Schwann cells that had been obtained from the sciatic nerves of donor animals, and had been either untreated or subjected to mechanical conditioning, were transplanted to the contused area of the cords following resection of the glial scar. Another group of animals was treated with glial scar excision only, and a fourth group had the contusion injury but neither glial excision nor transplantation. Scores according to the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale were assigned preoperatively and weekly thereafter. Tract tracing of descending and ascending spinal cord tracts was performed at six weeks postoperatively for quantitative histological evaluation of axonal regeneration.
While the recovery following glial scar excision without peripheral nerve transplantation was significantly worse than the recovery in the other groups, both transplantation groups had significantly higher BBB scores than the controls (no transplantation) in the early postoperative period (p < 0.05). Moreover, histological analysis showed markedly increased axonal regeneration at the lesional sites in the animals treated with the mechanically conditioned grafts than in the other groups (p < 0.05).
Functional recovery after spinal cord contusion improved following glial scar excision with transplantation of Schwann cells in peripheral nerve grafts to the contusion areas. Although recovery did not differ significantly between the transplantation groups, only the preconditioned grafts led to axonal regeneration at and past the lesional site. These grafts may further enhance functional recovery as the descending tracts eventually reach their target end-organs.
外周神经系统损伤后的恢复基于轴突与细胞外基质之间的促再生关系，这种关系由施万细胞建立。由于已证明对施万细胞进行机械调节可刺激其再生行为，我们试图确定将这些细胞移植到损伤后再生能力有限的中枢神经系统（即脊髓）是否会改善轴突再生和功能恢复。
用定向撞击器对48只成年Sprague-Dawley大鼠造成中度脊髓挫伤，在损伤后1周，对所有动物再次暴露脊髓。在其中24只动物中，将取自供体动物坐骨神经的带有施万细胞的周围神经移植物，在切除胶质瘢痕后移植到脊髓挫伤区域，这些施万细胞未处理或经过机械调节。另一组动物仅进行胶质瘢痕切除治疗，第四组动物有挫伤损伤但既未进行胶质切除也未进行移植。术前及此后每周根据Basso、Beattie、Bresnahan（BBB）运动评分量表进行评分。术后6周对脊髓的下行和上行束进行示踪，以对轴突再生进行定量组织学评估。
虽然未进行周围神经移植的胶质瘢痕切除后的恢复明显比其他组差，但两个移植组在术后早期的BBB评分均显著高于对照组（未移植）（p < 0.05）。此外，组织学分析显示，接受机械调节移植物治疗的动物损伤部位的轴突再生明显多于其他组（p < 0.05）。
脊髓挫伤后，通过将周围神经移植物中的施万细胞移植到挫伤区域并切除胶质瘢痕，功能恢复得到改善。虽然移植组之间的恢复没有显著差异，但只有预处理的移植物在损伤部位及损伤部位以外导致了轴突再生。随着下行束最终到达其目标终末器官，这些移植物可能会进一步增强功能恢复。
