Protective effect of topiramate on kainic acid-induced cell death in mice hippocampus.
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.
Park
Hae Jeong
HJ
Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Kim
Hak Jae
HJ
Park
Hi Joon
HJ
Ra
Jehyun
J
Zheng
Long Tai
LT
Yim
Sung Vin
SV
Chung
Joo-Ho
JH
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
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