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Protective effect of topiramate on kainic acid–induced cell death in mice hippocampus
Author(s) -
Park Hae Jeong,
Kim Hak Jae,
Park Hi Joon,
Ra Jehyun,
Zheng Long Tai,
Yim Sung Vin,
Chung JooHo
Publication year - 2008
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2007.01308.x
Subject(s) - kainic acid , hippocampal formation , hippocampus , topiramate , mapk/erk pathway , pharmacology , apoptosis , programmed cell death , chemistry , p38 mitogen activated protein kinases , neuroprotection , tunel assay , medicine , endocrinology , epilepsy , kinase , neuroscience , biology , biochemistry , glutamate receptor , receptor
SummaryThe 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 μg/5 μL, 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.