Proteins released from degenerating neurons are surrogate markers for acute brain damage.
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 14-3-3 zeta and 14-3-3 beta, 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.
Siman
Robert
R
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6084, USA. siman@pharm.med.upenn.edu
McIntosh
Tracy K
TK
Soltesz
Kristie M
KM
Chen
Zhaoming
Z
Neumar
Robert W
RW
Roberts
Victoria L
VL
D048948:14-3-3 Proteins; D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000473:pathology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009336:Necrosis; D009410:Nerve Degeneration / Q000134:cerebrospinal fluid* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D048948:14-3-3 Proteins; D015415:Biomarkers; D003598:Cytoskeletal Proteins; D010446:Peptide Fragments; D020543:Proteome; D014446:Tyrosine 3-Monooxygenase