Involvement of immune mechanism in the progressive brain damage

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 immnne response in the progressive brain damage are needed.