title: The immunosuppressant cyclosporin A inhibits recurrent seizures in an experimental model of temporal lobe epilepsy.
abstract: The immunosuppressant, cyclosporin A (CsA), is neuroprotective following brain injury. Previous studies suggest that CsA treatment ameliorates seizure severity during status epilepticus (SE) or cell death following SE. The antiepileptic effects of CsA on recurrent seizures, however, have not been investigated. In the present study, the effects of CsA on spontaneous recurrent seizures (SRSs) in a kainate (KA)-induced mouse model of mesial temporal lobe epilepsy (TLE) were examined. Moreover, the effects of CsA on epileptiform activity in a 4-aminopyridine (4-AP)-induced in vitro seizure model were investigated. A mesial TLE mouse model was generated with a unilateral intrahippocampal injection of KA. SRSs were determined in the ipsilateral hippocampal CA1 region with a long-term video-EEG. CsA was systemically administrated to the epileptic mice exhibiting a stable occurrence of SRSs. A 1-mg/kg dose of CsA did not have any effect on SRSs in the epileptic mice. However, a 5-mg/kg dose of CsA significantly reduced the number of SRSs and decreased the severity of the seizures in the epileptic mice. Additionally, CsA treatment inhibited spontaneous burst discharges in 4-AP-treated hippocampal slices. The results of the present study demonstrate that CsA inhibits recurrent seizures in a mouse model of mesial TLE and suggest that CsA may afford both neuroprotection against SE and antiepileptic effects during the chronic period of epilepsy.
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
authors.forename: Seungmoon
authors.initials: S
authors.lastname: Jung
authors.forename: Hyunwoo
authors.initials: H
authors.lastname: Yang
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Kim
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.forename: Daejong
authors.initials: D
authors.lastname: Jeon
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use*; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012008:Recurrence; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D015761:4-Aminopyridine; D007608:Kainic Acid