title: Neuroprotective Effects of Dexmedetomidine Against Hypoxia-Induced Nervous System Injury are Related to Inhibition of NF-κB/COX-2 Pathways.
abstract: 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.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China.
authors.forename: Wanying
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China.
authors.forename: Fuli
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Hua
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China.
authors.forename: Yueting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China. mlqiu11220@126.com.
authors.forename: Liqiu
authors.initials: L
authors.lastname: Mo
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D020927:Dexmedetomidine / Q000493:pharmacokinetics*; D000860:Hypoxia / Q000188:drug therapy*; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D020196:Trauma, Nervous System / Q000188:drug therapy*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D020927:Dexmedetomidine; D051546:Cyclooxygenase 2; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: COX-2; Dexmedetomidine; Hypoxia; NF-κB; Neuroprotection