Asanuma M, Ogawa N, Nishibayashi S, Kondo Y, Mori A
Department of Neuroscience, Okayama University Medical School, Japan.
Neurochem Res. 1995 Jan;20(1):101-5. doi: 10.1007/BF00995159.
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.
为了在动物模型中研究免疫系统与惊厥之间的关系，我们检测了反复给予免疫抑制剂环孢素A对戊四氮（PTZ）诱导的惊厥的影响，以及其结合蛋白亲环蛋白在大鼠脑中mRNA表达的变化。连续给予环孢素A（5mg/kg，皮下注射，共14天）显著加重了腹腔注射75mg/kg PTZ所诱导惊厥的严重程度。此外，它下调了几个脑区亲环蛋白mRNA的水平，并抑制了PTZ诱导的海马亲环蛋白mRNA的增加。与未进行PTZ预处理的组或PTZ预注射后给予慢性赋形剂的组相比，在首次注射PTZ后给予慢性环孢素A明显加重了第二次注射PTZ后的惊厥。有趣的是，在PTZ预处理组中，第二次注射PTZ后未发现单次注射PTZ后观察到的海马亲环蛋白mRNA的增加。因此，这些发现表明外周给予环孢素A可影响中枢神经系统，并且与首次惊厥发作相关的免疫反应在随后发作的严重程度中起关键作用。
