title: Protective effect of carbamazepine on kainic acid-induced neuronal cell death through activation of signal transducer and activator of transcription-3.
abstract: Studies have shown that the protective effect of carbamazepine (CBZ) on seizure-induced neuronal injury. However, its precise mechanisms remain unknown. Here, to investigate the neuroprotective mechanism of CBZ against seizure-induced neuronal cell death, we identified the change of gene expressions by CBZ in the hippocampus of kainic acid (KA)-treated mice using microarray method, and studied the involvement of candidate gene in neuroprotective action of CBZ. KA (15 mg/kg) and/or CBZ (30 mg/kg, 0.5 h after KA exposure) were injected intraperitoneally into mice. Through microarray analysis, we found that signal transducer and activator of transcription-3 (Stat3) gene expression was upregulated in the hippocampal CA3 region, 24 h after KA injection (15 mg/kg), and that CBZ further elevated Stat3 expression in KA-treated mice. KA also increased the protein level and phosphorylation of Stat3, and CBZ further increased the Stat3 phosphorylation, without changing Stat3 protein level in KA-treated mice. In particular, phospho-Stat3 immunoreactivity (IR) by KA was shown in astrocytes rather than in neurons; whereas phospho-Stat3 IR by CBZ in KA-treated mice was observed predominantly in neurons, and also in neuroprotective protein Bcl-xL-expression cells. These results indicate that Stat3 may play an important role in neuroprotective action of CBZ on seizure-induced neuronal injury.
authors: Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Hae Jeong
authors: HJ
authors: Park
authors: Su Kang
authors: SK
authors: Kim
authors: Joo-Ho
authors: JH
authors: Chung
authors: Jong Woo
authors: JW
authors: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D056654:CA3 Region, Hippocampal / Q000473:pathology; D002220:Carbamazepine / Q000494:pharmacology*; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D018696:Neuroprotective Agents; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D002220:Carbamazepine; D007608:Kainic Acid