Ogawa N, Asanuma M, Kondo Y
Department of Neuroscience, Okayama University Medical School, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1994 Oct;14(5):377-81.
No definitive evidence for the participation of the immune system in progressive brain damage has been previously reported. However, glial cells continue to accumulate after degeneration of neurons appears to be completed, and a recent study showed that microglia and leukocytes also accumulate after brain damage. Thus, it seemed possible that immune responses might play a role in the delayed effects. Cyclosporin A (CsA) is a cyclic undecapeptide of fungal origin with a strong immunosuppressive action but low myelotoxicity. We examined the effect of CsA administration on three different kinds of animal models for neurological deficits. Late onset reduction of muscarinic receptors after transient forebrain ischemia in gerbils was prevented by daily post-ischemic administration of CsA. This indicates that an immune mechanism may be involved in the progressive brain damage occurring after transient ischemia. On the other hand, CsA exacerbated iminodipropionitrile-induced dyskinesia both behaviorally and biochemically. CsA also mimicked pentylenetetrazol-induced seizures. These findings suggest that immune mechanisms may play important roles in the progression of brain damage and possibly that immunosuppressants might open a new chapter in the pathophysiology and treatment of chronic progressive neurodegenerative diseases. Further investigations on the immune response in the progressive brain damage are needed.
此前尚无关于免疫系统参与进行性脑损伤的确切证据报道。然而，在神经元变性似乎完成后，胶质细胞仍持续积累，并且最近一项研究表明，脑损伤后小胶质细胞和白细胞也会积累。因此，免疫反应可能在延迟效应中发挥作用似乎是有可能的。环孢素A（CsA）是一种源自真菌的环状十一肽，具有强大的免疫抑制作用但骨髓毒性较低。我们研究了给予CsA对三种不同的神经功能缺损动物模型的影响。通过在沙土鼠短暂性前脑缺血后每日给予CsA，可预防毒蕈碱受体的迟发性减少。这表明免疫机制可能参与了短暂性缺血后发生的进行性脑损伤。另一方面，CsA在行为和生化方面均加重了亚氨基二丙腈诱导的运动障碍。CsA还可模拟戊四氮诱导的癫痫发作。这些发现提示免疫机制可能在脑损伤的进展中起重要作用，并且免疫抑制剂可能会为慢性进行性神经退行性疾病的病理生理学和治疗开启新的篇章。需要对进行性脑损伤中的免疫反应进行进一步研究。
