title: Early Combined Therapy with Pharmacologically Induced Hypothermia and Edaravone Exerts Neuroprotective Effects in a Rat Model of Intracerebral Hemorrhage.
abstract: In present study, we evaluated acute neuroprotective effects of combined therapy with pharmacologically induced hypothermia and edaravone in a rat model of intracerebral hemorrhage (ICH). ICH was caused by injection of 0.5 U of collagenase VII to the caudate nucleus of male Sprague-Dawley rats. Sham-treated animals receive injections of normal saline instead of collagenase VII. All animals were randomly divided into five groups: sham group, ICH group, hypothermia group, edavarone (10 mg/kg) group, and combined hypothermia + edavarone group. Hypothermia was induced by injection of the second-generation neurotensin receptor agonist HPI-201 (2 mg/kg at 1 h after ICH; 1 mg/kg at 4 and 7 h after ICH). Hypothermia was sustained for at least 6 h. The study outcomes were the extent of brain edema, permeability of the blood-brain barrier (Evan's blue dye), expression of matrix metalloproteinase-9 and inflammatory cytokines (IL-1β, IL-4, IL-6, and TNF-α), and expression of apoptosis-related proteins (caspase-3, cytochrome C, Bcl-2, and Bax). Brain edema, permeability of the blood-brain barrier, and expression of metalloproteinase-9 were increased, while expression of caspase-3 and Bcl-2 was decreased by ICH. We observed that the combined therapy was significantly more potent in reverting the above negative trends induced by ICH. In conclusion, our results indicate that a combination of pharmacologically induced hypothermia and edavarone leads to potentiation of their respective neuroprotective effects.
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Road, Zhengzhou, 450014, Henan, China. drzhuyonglin@163.com.
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000473:pathology / Q000628:therapy*; D017364:Collagenases / Q000008:administration & dosage; D003131:Combined Modality Therapy; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D000077553:Edaravone; D007036:Hypothermia, Induced; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D010539:Permeability / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D000077553:Edaravone; D000983:Antipyrine
keywords: Apoptosis; Edaravone; Inflammation; Intracerebral hemorrhage; Neurological function; Pharmacologically induced hypothermia; Rats