Ubiquitin C-Terminal Hydrolase-L1 as a Biomarker for Ischemic and Traumatic Brain Injury in Rats

Abstract

Ubiquitin C-terminal hydrolase-L1 (UCH-L1), also called neuronal-specific protein gene product 9.5, is a highly abundant protein in the neuronal cell body and has been identified as a possible biomarker on the basis of a recent proteomic study. In this study, we examined whether UCH-L1 was significantly elevated in cerebrospinal fluid (CSF) following controlled cortical impact (CCI) and middle cerebral artery occlusion (MCAO; model of ischemic stroke) in rats. Quantitative immunoblots of rat CSF revealed a dramatic elevation of UCH-L1 protein 48 h after severe CCI and as early as 6 h after mild (30 min) and severe (2 h) MCAO. A sandwich enzyme-linked immunosorbent assay constructed to measure UCH-L1 sensitively and quantitatively showed that CSF UCH-L1 levels were significantly elevated as early as 2 h and up to 48 h after CCI. Similarly, UCH-L1 levels were also significantly elevated in CSF from 6 to 72 h after 30 min of MCAO and from 6 to 120 h after 2 h of MCAO. These data are comparable to the profile of the calpainproduced aII-spectrin breakdown product of 145 kDa biomarker. Importantly, serum UCH-L1 biomarker levels were also significantly elevated after CCI. Similarly, serum UCH-L1 levels in the 2-h MCAO group were significantly higher than those in the 30-min group. Taken together, these data from two rat models of acute brain injury strongly suggest that UCH-L1 is a candidate brain injury biomarker detectable in biofluid compartments (CSF and serum).

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2010
Accession Number
ADA528508

Entities

People

  • Dancia Scharf
  • Firas Kobeissy
  • Frank C. Tortella
  • Jitendra R. Dave
  • Jixiang Mo
  • Kevin K W Wang
  • Linda Papa
  • Linnet Akinyi
  • Ming C. Liu
  • Monika W. Oli
  • Ronald L. Hayes
  • Stephen F. Larner
  • Uwe Muller
  • Wenrong Zheng
  • Xi-chun Lu

Organizations

  • Walter Reed Army Institute of Research

Tags

DTIC Thesaurus Topics

  • Arteries
  • Blood
  • Brain Injuries
  • Cerebrovascular Disorders
  • Health Services
  • Medical Personnel
  • Neurodegeneration
  • Proteins
  • Wounds And Injuries

Fields of Study

  • Biology
  • Chemistry

Readers

  • Applied Combinatorial Optimization and Logic Circuit Design.
  • Cardiovascular Physiology
  • Molecular Biology and Genetics

Technology Areas

  • Biotechnology