Proteins released from degenerating neurons are surrogate markers for acute brain damage

被引:137
作者
Siman, R
McIntosh, TK
Soltesz, KM
Chen, ZM
Neumar, RW
Roberts, VL
机构
[1] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA
关键词
neurodegeneration; calpain; caspase; necrosis; apoptosis; cytoskeleton; cerebral ischemia; traumatic brain injury; 14-3-3; proteins; surrogate marker;
D O I
10.1016/j.nbd.2004.03.016
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The experimental and clinical study of degenerative brain disorders would benefit from new surrogate markers for brain damage. To identify novel candidate markers for acute brain injury, we report that rat cortical neurons release over 60 cytoskeletal and other proteins, as well as their proteolytic fragments into the medium during neuronal death. The profiles of released proteins differ for necrosis and apoptosis, although a subset of proteins is released generally during neurodegeneration. The value of this approach was established by immunodetection of the released proteins 14-3-3zeta and 14-3-3beta, as well as calpain and caspase derivatives of tau and alpha-spectrin in cerebrospinal fluid (CSF) following traumatic brain injury (TBI) or transient forebrain ischemia in the rat. These results indicate that proteins and their proteolytic fragments released from degenerating neurons are cerebrospinal fluid markers for acute brain damage and suggest that efflux of proteins from the injured brain may reflect underlying mechanisms for neurodegeneration. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:311 / 320
页数:10
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