A role for tumor necrosis factor α in death of dopaminergic neurons following neural transplantation

被引:42
作者
Clarke, DJ [1 ]
Branton, RL [1 ]
机构
[1] Dept Human Anat & Genet, Oxford OX1 3QX, England
基金
英国惠康基金;
关键词
cell death; dopaminergic; cytokines; neural transplantation; Parkinson's disease; TNFR1; ventral mesencephalon;
D O I
10.1006/exnr.2002.7911
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Poor survival of transplanted dopaminergic (DA) neurons remains a serious obstacle to the success of cell replacement therapy as an alternative to the current treatments for Parkinson's disease (PD). We have examined the temporal release profile of an inflammatory cytokine, tumor necrosis factor-alpha (TNFalpha), following transplantation of fetal mesencephalic tissue into the rat striatum. The amounts of TNFa released in vivo when added to cultures of embryonic DA neurons, significantly reduced the survival of DA neurons in vitro, and this cell death could be prevented by the inclusion of an antibody to the TNFalpha receptor type 1. Inclusion of this antibody in cell suspensions during transplantation also increased the survival of transplanted fetal DA neurons by approximately 250%. Use of this therapeutic antibody approach may offer significant improvements to neural transplantation as a treatment for PD. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:154 / 162
页数:9
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