title: Effects of Etanercept against Transient Cerebral Ischemia in Diabetic Rats.
abstract: Diabetes mellitus is known to exacerbate acute cerebral ischemic injury. Previous studies have demonstrated that infarction volumes caused by transient cerebral ischemia were greater in diabetic rats than in nondiabetic rats. Tumor necrosis factor-α (TNF-α) is a proinflammatory protein produced in the brain in response to cerebral ischemia that promotes apoptosis. Etanercept (ETN), a recombinant TNF receptor (p75)-Fc fusion protein, competitively inhibits TNF-α. Therefore, we evaluated the neuroprotective effects of chronic or acute treatment with ETN on cerebral injury caused by middle cerebral artery occlusion/reperfusion (MCAO/Re) in rats with streptozotocin-induced diabetes. Furthermore, we evaluated the effects of ETN against the apoptosis and myeloperoxidase activity. Single administration of ETN before MCAO significantly suppressed exacerbation of cerebral damage in nondiabetic rats, as assessed by infarct volume. In contrast, the diabetic state markedly aggravated MCAO/Re-induced cerebral damage despite ETN treatment within 24 h before MCAO. However, the damage was improved by repeated administration of ETN at 900 μg/kg/daily in rats in an induced diabetic state. These results suggested that repeated administration of ETN can prevent exacerbation of cerebral ischemic injury in the diabetic state and is mainly attributed to anti-inflammatory effects.
authors.affiliation: Laboratory of Immunobiochemistry, Department of Clinical Dietetics & Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Iwata
authors.affiliation: Laboratory of Immunobiochemistry, Department of Clinical Dietetics & Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Takayama
authors.affiliation: Laboratory of Organic and Medicinal Chemistry, School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Xuan
authors.affiliation: Laboratory of Immunobiochemistry, Department of Clinical Dietetics & Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kamiuchi
authors.affiliation: Laboratory of Pharmacology, School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsuzaki
authors.affiliation: Laboratory of Pharmacology, School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Okazaki
authors.affiliation: Laboratory of Immunobiochemistry, Department of Clinical Dietetics & Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hibino
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D000068800:Etanercept / Q000008:administration & dosage*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D018696:Neuroprotective Agents; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept