title: Glibenclamide enhances the effects of delayed hypothermia after experimental stroke in rats.
abstract: In order to evaluate whether glibenclamide can extend the therapeutic window during which induced hypothermia can protect against stroke, we subjected adult male Sprague-Dawley rats to middle cerebral artery occlusion (MCAO). We first verified the protective effects of hypothermia induced at 0, 2, 4 or 6h after MCAO onset, and then we assessed the effects of the combination of glibenclamide and hypothermia at 6, 8 or 10h after MCAO onset. At 24h after MCAO, we assessed brain edema, infarct volume, modified neurological severity score, Evans Blue leakage and expression of Sulfonylurea receptor 1 (SUR1) protein and pro-inflammatory factors. No protective effects were observed when hypothermia was induced too long after MCAO. At 6h after MCAO onset, hypothermia alone failed to decrease cerebral edema and infarct volume, but the combination of glibenclamide and hypothermia decreased both. The combination also improved neurological outcome, ameliorated blood-brain barrier damage and decreased levels of COX-2, TNF-α and IL-1β. These results suggest that glibenclamide enhances and extends the therapeutic effects of delayed hypothermia against ischemia stroke, potentially by ameliorating blood-brain barrier damage and declining levels of pro-inflammatory factors.
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Shu-Zhen
authors.initials: SZ
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Hu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Wang
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Lin
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zuo-Shan
authors.initials: ZS
authors.lastname: Xie
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: pansuyue82@126.com.
authors.forename: Su-Yue
authors.initials: SY
authors.lastname: Pan
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D005905:Glyburide / Q000008:administration & dosage*; D006979:Hyperthermia, Induced / Q000379:methods*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064233:Sulfonylurea Receptors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C577509:Abcc8 protein, rat; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D064233:Sulfonylurea Receptors; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D005905:Glyburide
keywords: Blood-brain barrier; Delayed hypothermia; Glibenclamide; Ischemic stroke; Pro-inflammatory factor