Disclosure: G.S. holds equity in EnCor Biotechnology Inc., a company commercializing certain of the antibodies and ELISAs used in this study, and may benefit by receiving royalties or equity growth.
Identification and preliminary characterization of ubiquitin C terminal hydrolase 1 (UCHL1) as a biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage†
Article first published online: 13 JAN 2010
Copyright © 2010 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 88, Issue 7, pages 1475–1484, 15 May 2010
How to Cite
Lewis, S. B., Wolper, R., Chi, Y.-Y., Miralia, L., Wang, Y., Yang, C. and Shaw, G. (2010), Identification and preliminary characterization of ubiquitin C terminal hydrolase 1 (UCHL1) as a biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage. J. Neurosci. Res., 88: 1475–1484. doi: 10.1002/jnr.22323
- Issue published online: 2 APR 2010
- Article first published online: 13 JAN 2010
- Manuscript Accepted: 13 OCT 2009
- Manuscript Revised: 12 OCT 2009
- Manuscript Received: 7 MAY 2009
- General Clinical Research Center. Grant Number: MO1-RR00082
- Departments of Neurosurgery and Neuroscience, McKnight Brain Institute, University of Florida College of Medicine
- EnCor Biotechnology Inc
- ubiquitin C-terminal hydrolase 1;
- aneurysmal subarachnoid hemorrhage;
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 S100β 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 S100β levels rapidly declined to baseline levels in 23 of 30 patients. Seven of thirty patients showed persistently elevated S100β 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 S100β 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 S100β 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. © 2010 Wiley-Liss, Inc.