title: Protective effect of topiramate on kainic acid-induced cell death in mice hippocampus.
abstract: The protective effect of topiramate (TPM) on seizure-induced neuronal injury is well known; however, its molecular basis has yet to be elucidated. We investigated the effect and signaling mediators of TPM on seizure-induced hippocampal cell death in kainic acid (KA)-treated ICR mice. KA-induced hippocampal cell death was identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Immunoreactivity (IR) of p-Erk, p-Jnk, p-P38, and caspase-3, and caspase-3 activity were observed in the hippocampal region 3 h after KA (0.1 microg/5 microL, i.c.v.) administration, and/or TPM (100 mg/kg, i.p.) pretreatment. TPM attenuated seizure-induced neuronal cell death and reduced KA-induced p-Erk IR in the CA3 region of the hippocampus, but did not affect p-Jnk and p-P38. In addition, TPM reduced caspase-3 IR and activation by KA. KA-induced seizures were also suppressed by TPM pretreatment. TPM inhibits seizures, and decreases Erk phosphorylation and caspase-3 activation by KA, thereby contributing to protection from neuronal injury.
authors.affiliation: Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hae Jeong
authors.initials: HJ
authors.lastname: Park
authors.forename: Hak Jae
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hi Joon
authors.initials: HJ
authors.lastname: Park
authors.forename: Jehyun
authors.initials: J
authors.lastname: Ra
authors.forename: Long Tai
authors.initials: LT
authors.lastname: Zheng
authors.forename: Sung Vin
authors.initials: SV
authors.lastname: Yim
authors.forename: Joo-Ho
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D048588:Benzoxazines; D015153:Blotting, Western; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling / Q000379:methods; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010078:Oxazines; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D000077236:Topiramate
chemical_list: D048588:Benzoxazines; D018696:Neuroprotective Agents; D010078:Oxazines; D000077236:Topiramate; C028911:cresyl violet; D005632:Fructose; D020930:MAP Kinase Kinase Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D007608:Kainic Acid