Department of Orthopaedics and Sports Medicine, University Medical Center, University of Washington School of Medicine, Seattle, WA 98195-6500, USA.
J Bone Joint Surg Am. 2010 Feb;92(2):396-403. doi: 10.2106/JBJS.I.00109.
Protective antiself response to nervous system injury has been reported to be mediated by a T-cell subpopulation that can recognize self-antigens. Immune cells have been shown to play a role in the regulation of motor neuron survival after a peripheral nerve injury. The objective of the present study was to evaluate the effects of immune system augmentation with use of the antigen glatiramer acetate, which is known to affect T-cell immunity, on peripheral nerve regeneration.
Wild-type and nude-type (T-cell-deficient) rats underwent crush injury of the sciatic nerve. Three and six weeks after the injury, the sciatic nerve was examined, both functionally (on the basis of footprint analysis and the tibialis anterior muscle response and weight) and histologically (on the basis of axon count).
Significantly greater muscle responses were measured after three weeks in the group of wild-type rats that were treated with glatiramer acetate (control limb:injured limb ratio, 0.05 for the glatiramer acetate group [n = 9], compared with 0.51 for the saline solution group [n = 8]; p < 0.05). Higher axon counts were also found in this group (control limb:injured limb ratio, -0.07 for the glatiramer acetate group [n = 10], compared with 0.29 for the saline solution group [n = 8]; p < 0.05). The nude-type rats showed no response to the intervention after three weeks but showed a delayed response after six weeks. A second dose of glatiramer acetate, delivered forty-eight hours after the injury, did not result in an improved response as compared with the control groups.
We found that a single treatment with glatiramer acetate resulted in accelerated functional and histological recovery after sciatic nerve crush injury. The role of T-cell immunity in the mechanism of glatiramer acetate was suggested by the partial and late response found in the T-cell-deficient rats.
据报道，神经系统损伤的保护性抗自体反应是由能够识别自身抗原的 T 细胞亚群介导的。免疫细胞已被证明在外周神经损伤后在调节运动神经元存活方面发挥作用。本研究的目的是评估使用已知影响 T 细胞免疫的抗原谷氨酸酯乙酸盐增强免疫系统对周围神经再生的影响。
野生型和裸鼠（T 细胞缺陷型）大鼠进行坐骨神经挤压伤。损伤后 3 周和 6 周，对坐骨神经进行检查，包括功能检查（基于足迹分析和胫骨前肌反应和重量）和组织学检查（基于轴突计数）。
在接受谷氨酸酯乙酸盐治疗的野生型大鼠组中，三周后肌肉反应明显更大（对照组：损伤组的比例为 0.05，谷氨酸酯乙酸盐组[n=9]，而生理盐水组[n=8]为 0.51；p<0.05）。该组的轴突计数也较高（对照组：损伤组的比例为-0.07，谷氨酸酯乙酸盐组[n=10]，而生理盐水组[n=8]为 0.29；p<0.05）。三周后，裸鼠对干预没有反应，但六周后出现延迟反应。损伤后四十八小时给予第二次谷氨酸酯乙酸盐剂量，与对照组相比，反应没有改善。
我们发现单次使用谷氨酸酯乙酸盐可加速坐骨神经挤压伤后的功能和组织学恢复。在 T 细胞缺陷型大鼠中发现的部分和延迟反应提示 T 细胞免疫在谷氨酸酯乙酸盐作用机制中的作用。
