Effects of repeated injection of cyclosporin A on pentylenetetrazol-induced convulsion and cyclophilin mRNA levels in rat brain

To investigate the relationship between the immune system and convulsions in an animal model, we examined the effects of repeated administration with the immunosuppressant cyclosporin A on pentylenetetrazol (PTZ)-induced convulsions and the changes in the mRNA expression of its binding protein cyclophilin in the rat brain. The consecutive administration of cyclosporin A (5 mg/kg s.c., 14 days) significantly aggravated the severity of convulsions induced with PTZ 75 mg/kg i.p. Furthermore, it down-regulated the levels of cyclophilin mRNA in several brain regions and inhibited the PTZ-induced increase of hippocampal cyclophilin mRNA. Compared with the group without PTZ pretreatment or the group treated with chronic vehicle administration after the PTZ-preinjection, chronic cyclosporin A administration after the initial injection of PTZ apparently aggravated convulsions after the second PTZ injection. Interestingly, the increase in hippocampal cyclophilin mRNA observed after a single PTZ injection was not found after the second PTZ injection in the group with PTZ pretreatment. Therefore, these findings suggest that cyclosporin A administered peripherally can affect the central nervous system, and that an immune response associated with the first convulsive episode plays a key role in severity during subsequent attacks.