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Int J Neurosci. 2015;125(12):936-40. doi: 10.3109/00207454.2014.980906. Epub 2014 Nov 25.

Soluble or soluble/membrane TNF-α inhibitors protect the brain from focal ischemic injury in rats.

Author information

1
a Unit of Psychiatry, Fundación Valle del Lili, Icesi University , Cali , Colombia.
2
b Department of Basic Sciences, School of Medicine, Caldas University , Manizales , Colombia.
3
c Department of Clinical Research, Unit of Clinical Pharmacology, Hospital General Universitario de Alicante, Miguel Hernández University , Alicante , Spain.
4
d Unit of Rheumatology, Fundación Valle del Lili, Icesi University , Cali , Colombia.
5
e Departament of Internal Medicine, Fundación Valle del Lili, CES University , Cali , Colombia.
6
f Faculty of Natural Sciences, Icesi University , Cali , Colombia.
7
g Unit of Neurology. Fundación Valle del Lili, Icesi University , Cali , Colombia, and.
8
h Faculty of Natural Sciences, Icesi University , Cali , Colombia.

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.

KEYWORDS:

anti TNF-α; brain ischemia; etanercept; experimental brain research; infliximab

PMID:
25350870
DOI:
10.3109/00207454.2014.980906
[Indexed for MEDLINE]

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