Ubiquitin C-Terminal Hydrolase-L1as a Biomarker for Ischemic and Traumatic Brain Injury in Rats

• Published in: The European journal of neuroscience Vol. 31; no. 4; pp. 722 - 732
• Main Authors: Liu, Ming Cheng, Akinyi, Linnet, Scharf, Danica, Mo, Jixiang, Larner, Stephen F., Muller, Uwe, Oli, Monika W., Zheng, WenRong, Kobeissy, Firas, Papa, Linda, Lu, Xi-Chun, Dave, Jitendra R., Tortella, Frank C, Hayes, Ronald L., Wang, Kevin K. W.
• Format: Journal Article
• Language: English
• Published: 01-02-2010
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2010.07097.x

Ubiquitin C-terminal hydrolase-L1 (UCH-L1), also called neuronal-specific protein gene product 9.5, is a highly abundant protein in neuronal cell body and has been identified as a possible biomarker based on recent proteomic study. In this study we examined whether UCH-L1 was significantly elevated in cerebrospinal fluid (CSF) following controlled cortical impact traumatic brain injury (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 (2h) MCAO. A sandwich ELISA constructed to measure UCH-L1 sensitively and quantitatively showed CSF UCH-L1 levels were significantly elevated as early as2hand out to 48h after CCI. Similarly, UCH-L1 levels were also significantly elevated in CSF from 6 h to 72 h after 30 min MCAO and from 6 to 120 h after 2 h MCAO. These data are comparable to the profile of the calpain-produced αII-spectrin breakdown productof145 kDa (SBDP145) 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).