IMMUNOSUPPRESSION IN NERVE ALLOGRAFTING - IS IT DESIRABLE
IMMUNOSUPPRESSION IN NERVE ALLOGRAFTING - IS IT DESIRABLE
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DOI：
10.1016/0022-510x(92)90146-c
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发表时间：
1992-10-01
影响因子：
4.4
通讯作者：
DAVEY, DF
中科院分区：
文献类型：
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作者：
ANSSELIN, AD;POLLARD, JD;DAVEY, DF
将免疫不相容的坐骨神经移植物植入Wistar大鼠的坐骨神经断端。为了诱导移植耐受，一些动物给予小剂量环孢素A(CsA)20周，然后逐渐停用。行为学、电生理学和组织学研究表明，无论治疗方法如何，所有动物都会发生一定程度的再生。每天5 mg/kg或10 mg/kg的剂量都不足以防止排斥反应和随后的同种异体移植物结构的破坏，因此，远端残端的神经再支配受到限制。这一点既表现在失神经足部功能恢复不佳，也表现在移植神经束的神经膜外发现大量再生轴突。因此，在这些剂量下不会诱导耐受性。此外，从实验动物和未手术(对照)动物记录的肌电振幅的显著降低表明，即使在如此低的剂量下，环孢素A也可能对未损伤的神经产生有害影响。因此，在进一步研究CsA的神经毒性之前，谨慎使用同种异体神经移植和CsA免疫抑制。这一点特别重要，因为CsA有时用于治疗某些神经病理性自身免疫性疾病。
Immunologically incompatible sciatic nerve grafts were inserted into the severed sciatic nerves of Wistar rats. In an attempt to induce graft tolerance, low-dose cyclosporin A (CsA) was administered to some animals for 20 weeks, then gradually withdrawn. Behavioural, electrophysiological and histological studies indicated that some degree of regeneration took place in all animals regardless of treatment. Neither a daily dose of 5 mg/kg nor 10 mg/kg was sufficient to prevent the rejection and subsequent disruption of allograft structure, and as a consequence reinnervation of the distal stump was limited. This was manifest both in the poor functional recovery of the denervated foot, and in the large number of regenerated axons found outside of the perineurial membranes of the transplanted fascicles. Therefore, tolerance was not induced at these doses. Furthermore, the significant decrease in the amplitude of electromyographs recorded from experimental and unoperated (control) animals suggests CsA may have a deleterious effect on unlesioned nerve even at these low doses. It would be prudent, therefore, to exercise caution in the combined use of nerve allografts and CsA immunosuppression, until the neurotoxicity of CsA has been investigated further. This is particularly important since CsA is sometimes used in the treatment of certain neuropathic autoimmune diseases.