Ubiquitin C-terminal hydrolase-L1 as a biomarker for ischemic and traumatic brain injury in rats.
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 calpain-produced alphaII-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).
Liu
Ming C
MC
Center of Innovative Research, Banyan Biomarkers, Inc., 12085 Research Drive, Alachua, FL 32615, USA.
Akinyi
Linnet
L
Scharf
Dancia
D
Mo
Jixiang
J
Larner
Stephen F
SF
Muller
Uwe
U
Oli
Monika W
MW
Zheng
Wenrong
W
Kobeissy
Firas
F
Papa
Linda
L
Lu
Xi-Chun
XC
Dave
Jitendra R
JR
Tortella
Frank C
FC
Hayes
Ronald L
RL
Wang
Kevin K W
KK
D000818:Animals; D015415:Biomarkers / Q000097:blood* / Q000134:cerebrospinal fluid*; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000097:blood* / Q000134:cerebrospinal fluid*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000097:blood* / Q000134:cerebrospinal fluid*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013049:Spectrin / Q000134:cerebrospinal fluid; D043222:Ubiquitin Thiolesterase / Q000097:blood* / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D013049:Spectrin; D043222:Ubiquitin Thiolesterase
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