Document Detail


Identification and preliminary characterization of ubiquitin C terminal hydrolase 1 (UCHL1) as a biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage.
MedLine Citation:
PMID:  20077430     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
By using two different approaches, ubiquitin C-terminal hydrolase 1 (UCHL1) was identified as a potential cerebrospinal fluid (CSF) biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage (ASAH) and presumably other CNS damage and disease states. Appropriate antibodies and a sensitive ELISA were generated, and the release of UCHL1 into CSF was compared with that of pNF-H and S100beta in a cohort of 30 ASAH patients. Both UCHL1 and pNF-H showed persistent release into CSF in almost all patients in the second week postaneurysmal rupture (AR), and S100beta levels rapidly declined to baseline levels in 23 of 30 patients. Seven of thirty patients showed persistently elevated S100beta levels over the first 5 days post-AR and also had relatively higher levels of pNF-H and UCHL1 higher compared with the rest. These patients proved to have very poor outcomes, with 6 of 7 expiring. Patients who did reduce S100beta levels tended to have a better outcome if pNF-H and UCHL1 levels were also lower, and elevated UCHL1 levels in the second week post-AR were particularly predictive of poor outcome. Acute coordinated releases of large amounts of UCHL1, pNF-H, and S100beta in 16 of 30 patients were observed, suggesting sudden loss of brain tissues associated with secondary events. We conclude that measurement of the CSF levels of these proteins reveals details of ASAH progression and recovery and predicts patient outcome.
Authors:
Stephen B Lewis; Regina Wolper; Yueh-Yun Chi; Lynn Miralia; Yong Wang; Cui Yang; Gerry Shaw
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  88     ISSN:  1097-4547     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-08     Completed Date:  2010-06-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1475-84     Citation Subset:  IM    
Copyright Information:
(c) 2010 Wiley-Liss, Inc.
Affiliation:
Department of Neurological Surgery, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Biological Markers / analysis,  cerebrospinal fluid
Brain Infarction / cerebrospinal fluid,  diagnosis,  enzymology
Cohort Studies
Enzyme-Linked Immunosorbent Assay
Female
Humans
Male
Middle Aged
Nerve Degeneration / cerebrospinal fluid*,  diagnosis,  enzymology*
Nerve Growth Factors / analysis,  cerebrospinal fluid
Neurofilament Proteins / analysis,  cerebrospinal fluid
Neurons / enzymology*,  pathology
Predictive Value of Tests
Prognosis
S100 Proteins / analysis,  cerebrospinal fluid
Subarachnoid Hemorrhage / complications*
Ubiquitin Thiolesterase / analysis,  cerebrospinal fluid*
Up-Regulation / physiology
Grant Support
ID/Acronym/Agency:
M01-RR00082/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Nerve Growth Factors; 0/Neurofilament Proteins; 0/S-100 calcium-binding protein beta subunit; 0/S100 Proteins; 108688-71-7/neurofilament protein H; EC 3.1.2.15/UCHL1 protein, human; EC 3.1.2.15/Ubiquitin Thiolesterase

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