title: Soluble or soluble/membrane TNF-α inhibitors protect the brain from focal ischemic injury in rats.
abstract: Tumor Necrosis Factor-alpha (TNF-α) is an immunomodulatory and proinflammatory cytokine implicated in neuro-inflammation and neuronal damage in response to cerebral ischemia. The present study tested the hypothesis that anti-TNF-α agents may be protective against cerebral infarction. Transient focal ischemia was artificially induced in anesthetized adult male Wistar rats (300-350 g) by middle cerebral artery occlusion (MCAO) with an intraluminal suture. TNF-α function was interfered with either a chimeric monoclonal antibody against TNF-α (infliximab-7 mg/kg) aiming to TNF-α soluble and membrane-attached form; or a chimeric fusion protein of TNF-α receptor-2 with a fragment crystallizable (Fc) region of IgG1 (etanercept-5 mg/kg) aiming for the TNF-α soluble form. Both agents were administered intraperitoneally 0 or 6 h after inducing ischemia. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. Cerebral infarct volume was significantly reduced in either etanercept or infliximab-treated group compared with non-treated MCAO rats 24 h after reperfusion. These results suggest that anti-TNF-α agents may reduce focal ischemic injury in rats.
authors.affiliation: a Unit of Psychiatry, Fundación Valle del Lili, Icesi University , Cali , Colombia.
authors.forename: C A
authors.initials: CA
authors.lastname: Arango-Dávila
authors.affiliation: b Department of Basic Sciences, School of Medicine, Caldas University , Manizales , Colombia.
authors.forename: A
authors.initials: A
authors.lastname: Vera
authors.affiliation: c Department of Clinical Research, Unit of Clinical Pharmacology, Hospital General Universitario de Alicante, Miguel Hernández University , Alicante , Spain.
authors.forename: A C
authors.initials: AC
authors.lastname: Londoño
authors.affiliation: d Unit of Rheumatology, Fundación Valle del Lili, Icesi University , Cali , Colombia.
authors.forename: A F
authors.initials: AF
authors.lastname: Echeverri
authors.affiliation: e Departament of Internal Medicine, Fundación Valle del Lili, CES University , Cali , Colombia.
authors.forename: F
authors.initials: F
authors.lastname: Cañas
authors.affiliation: f Faculty of Natural Sciences, Icesi University , Cali , Colombia.
authors.forename: C F
authors.initials: CF
authors.lastname: Cardozo
authors.affiliation: g Unit of Neurology. Fundación Valle del Lili, Icesi University , Cali , Colombia, and.
authors.forename: J L
authors.initials: JL
authors.lastname: Orozco
authors.affiliation: h Faculty of Natural Sciences, Icesi University , Cali , Colombia.
authors.forename: J
authors.initials: J
authors.lastname: Rengifo
authors.affiliation: d Unit of Rheumatology, Fundación Valle del Lili, Icesi University , Cali , Colombia.
authors.forename: C A
authors.initials: CA
authors.lastname: Cañas
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D000068800:Etanercept / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy; D000069285:Infliximab / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept
keywords: anti TNF-α; brain ischemia; etanercept; experimental brain research; infliximab