topiramate and cresyl-violet

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.

Topics: Animals; Apoptosis; Benzoxazines; Blotting, Western; Caspase 3; Cell Death; Cell Survival; Disease Models, Animal; Fructose; Hippocampus; Immunohistochemistry; In Situ Nick-End Labeling; Injections, Intraventricular; Kainic Acid; Male; MAP Kinase Kinase Kinases; Mice; Mice, Inbred ICR; Neurons; Neuroprotective Agents; Oxazines; Seizures; Topiramate