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

被引:41
作者
Arango-Davila, C. A. [1 ]
Vera, A. [2 ]
Londono, A. C. [3 ]
Echeverri, A. F. [4 ]
Canas, F. [5 ]
Cardozo, C. F. [6 ]
Orozco, J. L. [7 ]
Rengifo, J. [8 ]
Canas, C. A. [4 ]
机构
[1] Icesi Univ, Fdn Valle del Lili, Unit Psychiat, Cali, Colombia
[2] Caldas Univ, Sch Med, Dept Basic Sci, Manizales, Colombia
[3] Miguel Hernandez Univ, Clin Pharmacol Unit, Dept Clin Res, Hosp Gen Univ Alicante, Alicante, Spain
[4] Icesi Univ, Fdn Valle del Lili, Rheumatol Unit, Cali, Colombia
[5] CES Univ, Dept Internal Med, Fdn Valle del Lili, Cali, Colombia
[6] Icesi Univ, Fac Nat Sci, Cali, Colombia
[7] Icesi Univ, Fdn Valle del Lili, Neurol Unit, Cali, Colombia
[8] Icesi Univ, Fac Nat Sci, Cali, Colombia
关键词
brain ischemia; anti TNF-alpha; experimental brain research; etanercept; infliximab; NECROSIS-FACTOR-ALPHA; INFLAMMATORY RESPONSE; CEREBRAL-ISCHEMIA; SERUM-LEVELS; STROKE;
D O I
10.3109/00207454.2014.980906
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Tumor Necrosis Factor-alpha (TNF-alpha) 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-alpha 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-alpha function was interfered with either a chimeric monoclonal antibody against TNF-alpha (infliximab-7 mg/kg) aiming to TNF-alpha soluble and membrane-attached form; or a chimeric fusion protein of TNF-alpha receptor-2 with a fragment crystallizable (Fc) region of IgG1 (etanercept-5 mg/kg) aiming for the TNF-alpha 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-alpha agents may reduce focal ischemic injury in rats.
引用
收藏
页码:936 / 940
页数:5
相关论文
共 23 条
[1]   Exclusive tumor necrosis factor (TNF) signaling by the p75TNF receptor triggers inflammatory ischemia in the CNS of transgenic mice [J].
Akassoglou, K ;
Douni, E ;
Bauer, J ;
Lassmann, H ;
Kollias, G ;
Probert, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (02) :709-714
[2]  
Arango-Davila CA, 2002, SALUD UIS, V34, P195
[3]   Tumor necrosis factor-alpha - A mediator of focal ischemic brain injury [J].
Barone, FC ;
Arvin, B ;
White, RF ;
Miller, A ;
Webb, CL ;
Willette, RN ;
Lysko, PG ;
Feuerstein, GZ .
STROKE, 1997, 28 (06) :1233-1244
[4]   Selective targeting of a TNFR decoy receptor pharmaceutical to the primate brain as a receptor-specific IgG fusion protein [J].
Boado, Ruben J. ;
Hui, Eric Ka-Wai ;
Lu, Jeff Zhiqiang ;
Zhou, Qing-Hui ;
Pardridge, William M. .
JOURNAL OF BIOTECHNOLOGY, 2010, 146 (1-2) :84-91
[5]   Foundation review: Current therapies in ischemic stroke. Part B. Future candidates in stroke therapy and experimental studies [J].
Broussalis, Erasmia ;
Trinka, Eugen ;
Killer, Monika ;
Harrer, Andrea ;
McCoy, Mark ;
Kraus, Joerg .
DRUG DISCOVERY TODAY, 2012, 17 (13-14) :671-684
[6]  
Domaç FM, 2007, NEUROSCIENCES, V12, P25
[7]   Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production [J].
Emsley, Hedley C. A. ;
Smith, Craig J. ;
Gavin, Carole M. ;
Georgiou, Rachel F. ;
Vail, Andy ;
Barberan, Elisa M. ;
Illingworth, Karen ;
Scarth, Sylvia ;
Wickramasinghe, Vijitha ;
Hoadley, Margaret E. ;
Rothwell, Nancy J. ;
Tyrrell, Pippa J. ;
Hopkins, Stephen J. .
BMC NEUROLOGY, 2007, 7 (1)
[8]   Neurodegenerative and neuroprotective effects of tumor necrosis factor (TNF) in retinal ischemia: Opposite roles of TNF receptor 1 and TNF receptor 2 [J].
Fontaine, V ;
Mohand-Said, S ;
Hanoteau, N ;
Fuchs, L ;
Pfizenmaier, K ;
Eisel, U .
JOURNAL OF NEUROSCIENCE, 2002, 22 (07)
[9]   Ischemic and excitotoxic brain injury is enhanced in mice lacking the p55 tumor necrosis factor receptor [J].
Gary, DS ;
Bruce-Keller, AJ ;
Kindy, MS ;
Mattson, MP .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1998, 18 (12) :1283-1287
[10]   Tumor necrosis factor-α neutralization reduced cerebral edema through inhibition of matrix metalloproteinase production after transient focal cerebral ischemia [J].
Hosomi, N ;
Ban, CR ;
Naya, T ;
Takahashi, T ;
Guo, P ;
Song, XYR ;
Kohno, M .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2005, 25 (08) :959-967