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

Masato Asanuma, Norio Ogawa, Sakiko Nishibayashi, Yoichi Kondo, Akitane Mori

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10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)101-105
Number of pages5
JournalNeurochemical Research
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 1 1995

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Keywords

  • Cyclosporin A
  • convulsion
  • cyclophilin
  • pentylenetetrazol
  • rat brain
  • seizures

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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