Neuroprotective effects of TNF binding protein in focal cerebral ischemia

被引:127
作者
Nawashiro, H
Martin, D
Hallenbeck, JM
机构
[1] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA
[2] Amgen Inc, Dept Pharmacol, Boulder, CO USA
关键词
tumor necrosis factor; TNF binding protein; brain infarction; mouse; DNA fragmentation;
D O I
10.1016/S0006-8993(97)00981-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The effect of tumor necrosis factor binding protein (TFNbp) was studied in mice subjected to a permanent middle cerebral artery occlusion (MCAO). TNFbp is a dimeric form of the type I soluble TNF receptor linked to polyethylene glycol (TNFbp), and binds and inhibits TNF-alpha. TNFbp produced a significant reduction in the cortical infarct volume (22.6 +/- 3.5 mm(3) immediately after MCAO; 25.2 +/- 2.4 mm(3) 1 h after MCAO) compared with vehicle-treated animals (30.3 +/- 3.7 mm(3) immediately post MCAO; 31 +/- 3.7 mm(3) 1 h after MCAO (mean +/- S.D.) when administered intracranially up to 60 min post-occlusion. The neuroprotective effect of TNFbp was sustained in mice for 2 weeks after MCAO. DNA fragmentation at the margin of the cortical infarcts was dramatically reduced in mice treated with TNFbp whereas all control animals showed consistent and obvious DNA fragmentation 2 weeks after MCAO. TNFbp could have therapeutic value for the treatment of ischemic stroke if the problem of delivery to brain can be overcome. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:265 / 271
页数:7
相关论文
共 23 条
[1]   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
[2]  
BRISCOE DM, 1992, J IMMUNOL, V149, P2954
[3]   Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat [J].
Buttini, M ;
Appel, K ;
Sauter, A ;
GebickeHaerter, PJ ;
Boddeke, HWGM .
NEUROSCIENCE, 1996, 71 (01) :1-16
[4]   ALPHA-PHENYL-TERT-BUTYL-NITRONE REDUCES CORTICAL INFARCT AND EDEMA IN RATS SUBJECTED TO FOCAL ISCHEMIA [J].
CAO, XH ;
PHILLIS, JW .
BRAIN RESEARCH, 1994, 644 (02) :267-272
[5]   Inhibition of tumor necrosis factor-alpha reduces focal cerebral ischemic injury in the spontaneously hypertensive rat [J].
Dawson, DA ;
Martin, D ;
Hallenbeck, JM .
NEUROSCIENCE LETTERS, 1996, 218 (01) :41-44
[6]   EARLY EVENTS IN THE ANTIPROLIFERATIVE ACTION OF TUMOR NECROSIS FACTOR ARE SIMILAR TO THE EARLY EVENTS IN EPIDERMAL GROWTH-FACTOR GROWTH-STIMULATION [J].
DONATO, NJ ;
INCE, C ;
ROSENBLUM, MG ;
GALLICK, GE .
JOURNAL OF CELLULAR BIOCHEMISTRY, 1989, 41 (03) :139-157
[7]   Apoptosis as a mechanism of lectin-dependent monocyte-mediated cytotoxicity [J].
Dong, HD ;
Kimoto, Y ;
Takai, S ;
Taguchi, T .
IMMUNOLOGICAL INVESTIGATIONS, 1996, 25 (1-2) :65-78
[8]  
FEUERSTEIN GZ, 1994, CEREBROVAS BRAIN MET, V6, P341
[9]  
GARCIA JH, 1995, AM J PATHOL, V147, P1477
[10]   TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways [J].
Hsu, HL ;
Shu, HB ;
Pan, MG ;
Goeddel, DV .
CELL, 1996, 84 (02) :299-308