Neuroprotective Effects of Dexmedetomidine Against Hypoxia-Induced Nervous System Injury are Related to Inhibition of NF-κB/COX-2 Pathways
| Autor: | Liqiu Mo, Fuli Yuan, Wanying Pan, Lin Lin, Xiaoxiao Hua, Nan Zhang, Yueting Wang |
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| Rok vydání: | 2015 |
| Předmět: |
Male
0301 basic medicine Pharmacology Neuroprotection 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation medicine Animals Trauma Nervous System Dexmedetomidine Hypoxia Caspase 3 business.industry NF-kappa B Neurotoxicity Antagonist Atipamezole NF-κB Cell Biology General Medicine Hypoxia (medical) medicine.disease Up-Regulation Mice Inbred C57BL Neuroprotective Agents 030104 developmental biology chemistry Cyclooxygenase 2 medicine.symptom business 030217 neurology & neurosurgery Signal Transduction medicine.drug |
| Zdroj: | Cellular and Molecular Neurobiology. 36:1179-1188 |
| ISSN: | 1573-6830 0272-4340 |
| Popis: | Dexmedetomidine has been reported to provide neuroprotection against hypoxia-induced damage. However, the underlying mechanisms remain unclear. We examined whether dexmedetomidine's neuroprotective effects were mediated by the NF-κB/COX-2 pathways. Adult male C57BL/6 mice were subjected to a 30-min hypoxic treatment followed by recovery to normal conditions. They received dexmedetomidine (16 or 160 μg/kg) or 25 mg/kg atipamezole, an α2-adrenoreceptor antagonist, intraperitoneally before exposure to hypoxia. The whole brain was harvested 6, 18, or 36 h after the hypoxia to determine the histopathological outcome and cleaved caspase-3, Bax/Bcl, NF-κB, and COX-2 levels. Hypoxia treatment induced significant neurotoxicity, including destruction of the tissue structure and upregulation of the protein levels of caspase-3, the ratio of Bax/Bcl-2, NF-κB, and COX-2. Dexmedetomidine pretreatment effectively improved histological outcome and restored levels of caspase-3, the Bax/Bcl-2 ratio, NF-κB, and COX-2. Atipamezole reversed the neuroprotection induced by dexmedetomidine. Neuroprotection was achieved by PDTC and NS-398, inhibitors of NF-κB and COX-2, respectively. Dexmedetomidine use before hypoxia provides neuroprotection. Inhibition of NF-κB/COX-2 pathways activation may contribute to the neuroprotection of dexmedetomidine. |
| Databáze: | OpenAIRE |
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