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Protective Effect of Carbamazepine on Kainic Acid-induced Neuronal Cell Death Through Activation of Signal Transducer and Activator of Transcription-3

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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.

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Acknowledgements

This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A100768).

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  1. Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea

    Hae Jeong Park, Su Kang Kim & Joo-Ho Chung

  2. Department of Neuropsychiatry, School of Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea

    Jong Woo Kim

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Correspondence to Jong Woo Kim.

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Park, H.J., Kim, S.K., Chung, JH. et al. Protective Effect of Carbamazepine on Kainic Acid-induced Neuronal Cell Death Through Activation of Signal Transducer and Activator of Transcription-3. J Mol Neurosci 49, 172–181 (2013). https://doi.org/10.1007/s12031-012-9854-x

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