title: Single administration of soluble epoxide hydrolase inhibitor suppresses neuroinflammation and improves neuronal damage after cardiac arrest in mice.
abstract: Cardiac arrest (CA) causes ischemia-reperfusion injury in the whole body among victims. Especially in the brain, inflammation and neuronal cell death can lead to irreversible dysfunction. Our goal was to determine whether a single administration of soluble epoxide hydrolase inhibitor (AS2586144-CL) has a neuroprotective effect and decreases the inflammatory response after CA and cardiopulmonary resuscitation (CPR). Global cerebral ischemia was induced in male C57BL/6 mice with 8min of CA. Thirty minutes after recovery of spontaneous circulation, the mice were randomly assigned to three groups and administered AS2586144-CL: 1mg/kg (n=25), 10mg/kg (n=25), or 0mg/kg (vehicle, n=25). At 6 and 7 days after CA/CPR, behavioral tests were conducted and brains were removed for histological evaluation. Analysis of histological damage 7 days after CA/CPR revealed that 10mg/kg of AS2586144-CL protected neurons, and suppressed cytokine production and microglial migration into the hippocampus. Two hours after CA/CPR, 10mg/kg of AS2586144-CL suppressed serum tumor necrosis factor-α and hippocampal nuclear factor κB expression. Our data show that 10mg/kg of AS2586144-CL administered following CA/CPR suppresses inflammation and decreases neuronal damage.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Tsukuba, 1-1-1 Tennodai, Ibaraki, Japan. Electronic address: taguchine@gmail.com.
authors.forename: Noriko
authors.initials: N
authors.lastname: Taguchi
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Tsukuba, 1-1-1 Tennodai, Ibaraki, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Nakayama
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Tsukuba, 1-1-1 Tennodai, Ibaraki, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D016887:Cardiopulmonary Resuscitation; D016207:Cytokines / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D006323:Heart Arrest / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C000589444:3-cyclopropyl-4-(4-(2-(((6,6-dimethylbicyclo(3.1.1)heptan-2-yl)methyl)amino)-2-oxoethyl)piperidin-1-yl)benzoic acid; D001565:Benzoates; D001643:Bridged Bicyclo Compounds; D016207:Cytokines; D018696:Neuroprotective Agents; D004851:Epoxide Hydrolases
keywords: Brain ischemia; Cardiac arrest; Hippocampus; Microglia; Neuroprotection; sEH inhibitor