title: Effects of repeated injection of cyclosporin A on pentylenetetrazol-induced convulsion and cyclophilin mRNA levels in rat brain.
abstract: 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.
authors.affiliation: Department of Neuroscience, Okayama University Medical School, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Asanuma
authors.forename: N
authors.initials: N
authors.lastname: Ogawa
authors.forename: S
authors.initials: S
authors.lastname: Nishibayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
authors.forename: A
authors.initials: A
authors.lastname: Mori
mesh_terms: D000591:Amino Acid Isomerases / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D016572:Cyclosporine / Q000494:pharmacology*; D004334:Drug Administration Schedule; D008297:Male; D008969:Molecular Sequence Data; D010433:Pentylenetetrazole; D019696:Peptidylprolyl Isomerase; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology
chemical_list: D002352:Carrier Proteins; D012333:RNA, Messenger; D016572:Cyclosporine; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D010433:Pentylenetetrazole