Becker M, Schaller E, Walter G F, Berger A
Klinik für Plastische, Hand- und Wiederherstellungschirurgie, Medizinischen Hochschule Hannover.
Handchir Mikrochir Plast Chir. 1990 Jul;22(4):196-202.
Since the introduction of Cyclosporine A (CsA) in 1972, several studies have focused on its effects on experimental autologous peripheral nerve transplants. Although several studies have reported neurotoxicity of CsA in the central nervous system, no such data exist regarding the peripheral nervous system. The present study focuses on the effects of CsA in the therapeutic and toxic doses on axon regeneration, particularly the rate and quality of axon regeneration. Autologous nerve transplantation was performed in Lewis rats and axon regeneration evaluated clinically (motor function, body weight), electroneurographically and histologically. In transplanted nerves, even high doses of CsA (30 mg/kg bodyweight) did not lead to delayed or impaired axon regeneration. Long-term application in normal peripheral nerves did however cause axon degeneration with edema and vacuolisation of myelin sheaths, retraction of myelin sheaths from the node of Ranvier, and marked enhancement of the Schmidt-Lantermann incisures. As neurological side effects such as tremor and paresthesia have been reported under application of CsA in man, the above data might be of clinical relevance.
自1972年环孢素A(CsA)问世以来,多项研究聚焦于其对实验性自体周围神经移植的影响。尽管有多项研究报道了CsA对中枢神经系统的神经毒性,但关于周围神经系统尚无此类数据。本研究重点关注治疗剂量和中毒剂量的CsA对轴突再生的影响,特别是轴突再生的速度和质量。在Lewis大鼠中进行自体神经移植,并通过临床评估(运动功能、体重)、神经电图和组织学评估轴突再生情况。在移植神经中,即使是高剂量的CsA(30毫克/千克体重)也不会导致轴突再生延迟或受损。然而,在正常周围神经中长期应用CsA会导致轴突变性,伴有髓鞘水肿和空泡化、髓鞘从郎飞结退缩以及施密特-兰特尔曼切迹明显增多。由于在人体应用CsA时曾有震颤和感觉异常等神经副作用的报道,上述数据可能具有临床相关性。