Kvist Martin, Kanje Martin, Ekberg Henrik, Corbascio Matthias, Dahlin Lars B
Department of Clinical Sciences/Hand Surgery, Malmö University Hospital, Malmö, Sweden.
J Peripher Nerv Syst. 2008 Sep;13(3):200-7. doi: 10.1111/j.1529-8027.2008.00178.x.
Costimulation blockade can prevent rejection of nerve allografts in short-term studies. We tested if costimulation blockade also prevented rejection of nerve allografts in long-term experiments, thereby improving functional recovery. A 7-mm sciatic nerve defect in C57/BL6 mice was bridged either by nerve allografts from Balb/C mice or by isogenic nerve grafts (isografts) from C57/BL6 mice. Costimulation blockade in the form of a triple treatment with anti-LFA-1, anti-CD40L, and CTLA4Ig was given at post-operative days 0, 2, 4, and 6 (intraperitoneal). Control mice (placebo; allografts) with nerve grafts were treated with isotype antibodies during the same time period. After 49 days, tetanic muscle force, wet weight of gastrocnemius muscle, histology, and morphometry in the tibial nerve were evaluated. Costimulation blockade diminished rejection of the nerve allografts. Axons bridged the graft. Treatment increased wet weight of the gastrocnemius muscle and resulted in a higher mean myelin area/nerve fiber in the tibial nerve distal to the nerve grafts. Tetanic muscle force and number of axons in tibial nerve showed no differences between groups. We conclude that rejection is suppressed by costimulation blockade. Treatment improves recovery of target muscle and myelination after nerve allografting.
在短期研究中，共刺激阻断可预防神经同种异体移植的排斥反应。我们测试了在长期实验中共刺激阻断是否也能预防神经同种异体移植的排斥反应，从而改善功能恢复。通过植入来自Balb/C小鼠的神经同种异体移植物或来自C57/BL6小鼠的同基因神经移植物（同系移植物）来桥接C57/BL6小鼠7毫米的坐骨神经缺损。在术后第0、2、4和6天（腹腔内）给予抗LFA-1、抗CD40L和CTLA4Ig三联治疗形式的共刺激阻断。在同一时期，用同型抗体治疗接受神经移植物的对照小鼠（安慰剂；同种异体移植物）。49天后，评估强直肌肉力量、腓肠肌湿重、组织学以及胫神经的形态测量。共刺激阻断减少了神经同种异体移植的排斥反应。轴突穿过移植物。治疗增加了腓肠肌的湿重，并导致神经移植物远端胫神经中平均髓鞘面积/神经纤维更高。各组之间的强直肌肉力量和胫神经中的轴突数量没有差异。我们得出结论，共刺激阻断可抑制排斥反应。治疗可改善神经同种异体移植后靶肌肉的恢复和髓鞘形成。
