title: 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 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).
authors.affiliation: Center of Innovative Research, Banyan Biomarkers, Inc., 12085 Research Drive, Alachua, FL 32615, USA.
authors.forename: Ming C
authors.initials: MC
authors.lastname: Liu
authors.forename: Linnet
authors.initials: L
authors.lastname: Akinyi
authors.forename: Dancia
authors.initials: D
authors.lastname: Scharf
authors.forename: Jixiang
authors.initials: J
authors.lastname: Mo
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Larner
authors.forename: Uwe
authors.initials: U
authors.lastname: Muller
authors.forename: Monika W
authors.initials: MW
authors.lastname: Oli
authors.forename: Wenrong
authors.initials: W
authors.lastname: Zheng
authors.forename: Firas
authors.initials: F
authors.lastname: Kobeissy
authors.forename: Linda
authors.initials: L
authors.lastname: Papa
authors.forename: Xi-Chun
authors.initials: XC
authors.lastname: Lu
authors.forename: Jitendra R
authors.initials: JR
authors.lastname: Dave
authors.forename: Frank C
authors.initials: FC
authors.lastname: Tortella
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hayes
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
mesh_terms: 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*
chemical_list: D015415:Biomarkers; D013049:Spectrin; D043222:Ubiquitin Thiolesterase
references.citation: Neuron. 1988 Jun;1(4):279-87
references.pmid: 2856162
references.citation: Neurochem Int. 2000 Oct;37(4):351-61
references.pmid: 10825575
references.citation: J Neurotrauma. 2004 Nov;21(11):1553-61
references.pmid: 15684648
references.citation: J Neurotrauma. 2007 Dec;24(12):1793-801
references.pmid: 18159990
references.citation: Biochem Biophys Res Commun. 2005 Nov 4;336(4):1268-77
references.pmid: 16176808
references.citation: Biochemistry. 1996 May 28;35(21):6735-44
references.pmid: 8639624
references.citation: J Neurosci. 1989 May;9(5):1579-90
references.pmid: 2542478
references.citation: Restor Neurol Neurosci. 2003;21(3-4):171-6
references.pmid: 14530579
references.citation: J Neurosurg. 2005 Jul;103(1 Suppl):61-8
references.pmid: 16122007
references.citation: J Cereb Blood Flow Metab. 2001 Jul;21(7):865-75
references.pmid: 11435799
references.citation: Acta Neurochir (Wien). 2008 Mar;150(3):221-7; discussion 227
references.pmid: 18193148
references.citation: Brain Res. 2008 Jun 5;1213:1-11
references.pmid: 18456245
references.citation: Trends Neurosci. 1999 Sep;22(9):391-7
references.pmid: 10441299
references.citation: Nat Neurosci. 2002 Nov;5 Suppl:1023-5
references.pmid: 12403975
references.citation: J Trauma. 2008 Oct;65(4):778-82; discussion 782-4
references.pmid: 18849790
references.citation: Acta Neurol Scand. 2001 Nov;104(5):288-95
references.pmid: 11696023
references.citation: J Neurotrauma. 2000 Aug;17(8):641-7
references.pmid: 10972241
references.citation: Neurobiol Dis. 2004 Jul;16(2):311-20
references.pmid: 15193288
references.citation: Nat Genet. 1999 Sep;23(1):47-51
references.pmid: 10471497
references.citation: Br J Neurosurg. 1999 Feb;13(1):56-9
references.pmid: 10492686
references.citation: J Neuropathol Exp Neurol. 2009 Mar;68(3):241-9
references.pmid: 19225412
references.citation: Biochemistry. 1998 Mar 10;37(10):3358-68
references.pmid: 9521656
references.citation: Clin Chem. 2003 Oct;49(10):1752-62
references.pmid: 14500616
references.citation: Biol Reprod. 2005 Jul;73(1):29-35
references.pmid: 15744022
references.citation: Pediatrics. 2006 Feb;117(2):325-32
references.pmid: 16452350
references.citation: Brain Res. 1988 Sep 13;460(1):189-94
references.pmid: 2905922
references.citation: Biochem Soc Trans. 1992 Aug;20(3):631-7
references.pmid: 1426603
references.citation: Ann N Y Acad Sci. 1993 May 28;679:78-86
references.pmid: 8512209
references.citation: Neurol Res. 2001 Mar-Apr;23(2-3):190-2
references.pmid: 11320598
references.citation: Br J Neurosurg. 1996 Oct;10(5):471-6
references.pmid: 8922706
references.citation: J Neurotrauma. 2008 Sep;25(9):1079-85
references.pmid: 18729720
references.citation: Neuroreport. 1998 Aug 3;9(11):2437-42
references.pmid: 9721910
references.citation: Stroke. 1997 Oct;28(10):1956-60
references.pmid: 9341703
references.citation: J Trauma. 2004 Nov;57(5):1006-12
references.pmid: 15580024
references.citation: Ann Thorac Surg. 2000 Mar;69(3):750-4
references.pmid: 10750755
references.citation: J Cereb Blood Flow Metab. 2004 Jan;24(1):98-106
references.pmid: 14688621
references.citation: J Neurotrauma. 2007 Feb;24(2):354-66
references.pmid: 17375999
references.citation: Shock. 2005 Aug;24(2):119-23
references.pmid: 16044081
references.citation: Neuroreport. 1999 Feb 5;10(2):427-9
references.pmid: 10203348
references.citation: Physiol Behav. 2003 Nov;80(2-3):167-75
references.pmid: 14637213
references.citation: Br J Anaesth. 2003 Oct;91(4):595-7
references.pmid: 14504167
references.citation: J Neurol Neurosurg Psychiatry. 2006 Jun;77(6):753-9
references.pmid: 16705199
references.citation: Brain Res. 2002 Aug 23;947(1):131-9
references.pmid: 12144861
references.citation: J Alzheimers Dis. 2007 May;11(2):153-64
references.pmid: 17522440
references.citation: EMBO J. 1999 Jul 15;18(14):3877-87
references.pmid: 10406793
references.citation: Expert Rev Proteomics. 2005 Aug;2(4):603-14
references.pmid: 16097892
references.citation: J Cereb Blood Flow Metab. 2005 Nov;25(11):1433-44
references.pmid: 15902199
references.citation: J Neurol Sci. 1981 Mar;49(3):429-38
references.pmid: 7217993
references.citation: Shock. 2004 Jan;21(1):72-6
references.pmid: 14676687
references.citation: J Neurotrauma. 2004 Oct;21(10):1443-56
references.pmid: 15672634
references.citation: J Immunol Methods. 2007 Jan 30;319(1-2):34-40
references.pmid: 17140597
references.citation: Brain Res. 1989 Jul 17;492(1-2):366-70
references.pmid: 2546656
references.citation: J Neurochem. 2001 Sep;78(6):1297-306
references.pmid: 11579138
references.citation: Mol Cell Biol. 2000 Jul;20(13):4691-8
references.pmid: 10848595
references.citation: Mol Cell Proteomics. 2006 Oct;5(10):1887-98
references.pmid: 16801361
references.citation: Stroke. 2007 Dec;38(12):3230-6
references.pmid: 17975104
references.citation: J Neurol Sci. 2005 Jun 15;233(1-2):183-98
references.pmid: 15896809
references.citation: Ann Emerg Med. 2002 Mar;39(3):254-7
references.pmid: 11867977
references.citation: Surg Neurol. 1995 Mar;43(3):267-70; discussion 270-1
references.pmid: 7540773
references.citation: FASEB J. 1997 Dec;11(14):1245-56
references.pmid: 9409543
references.citation: Neurology. 2004 Apr 27;62(8):1303-10
references.pmid: 15111666