title: Temporal Profile and Severity Correlation of a Panel of Rat Spinal Cord Injury Protein Biomarkers.
abstract: In the USA, there are approximately 12,000 new cases of spinal cord injury (SCI) each year and some 1.2 million people living with paralysis due to SCI. Seven percent of them are paralyzed due to an accident or injury occurring while serving in the military. Here, we report a systematic study on protein biomarker candidates in a rat SCI model with either moderate or severe injury. Tissue, cerebrospinal fluid (CSF), and serum samples were obtained at 4 h, 24 h, and 7 days post-injury. The candidate biomarkers included axonal injury markers αII-spectrin breakdown products (SBDP150/145/120), neuronal cell body injury marker ubiquitin C-terminal hydrolase-L1 (UCH-L1), astrogliosis/astroglial injury markers S100 calcium-binding protein-β (S100β), glial fibrillary acidic protein (GFAP) and GFAP breakdown products (GBDPs), demyelination marker myelin basic protein (MBP), axonal injury marker phosphorylated neurofilament-H (pNF-H), and neuroinflammation marker interleukin-6 (IL-6). SBDP150/145, UCH-L1, GFAP, and S100β were found as acute biomarkers with significantly elevated levels within 24 h. GBDP44, GBDP38, and pNF-H are acute and subacute biomarkers that were found to have increased at 4 h, 24 h, and 7 days. MBP and SBDP120 were considered subacute biomarkers which were only detectable at 7 days post-injury. These results not only allow us to gain important insight into the patho-mechanisms of SCI but also showcase the possibility of using some of the protein biomarkers to track injury severity and disease progression and resolution. These biomarkers can potentially serve as tools that assist therapy development and clinical trials.
authors.affiliation: Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA. zhihuiyang@ufl.edu.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Yang
authors.affiliation: University of Miami Leonard M. Miller School of Medicine, Miami, FL, 33136, USA.|Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL, 33125, USA.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Bramlett
authors.affiliation: Physiological Sciences and Chemistry, University of Florida, Gainesville, FL, 32611, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Moghieb
authors.affiliation: Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA.|Guangdong General Hospital, Guangzhou, Guangdong, 510080, China.
authors.forename: Dongnan
authors.initials: D
authors.lastname: Yu
authors.affiliation: Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA.|School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Lin
authors.affiliation: Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Bauer
authors.affiliation: Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA.
authors.forename: Tyler M
authors.initials: TM
authors.lastname: Selig
authors.affiliation: Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Jaalouk
authors.affiliation: Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA.
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Weissman
authors.affiliation: Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA.
authors.forename: Disa S
authors.initials: DS
authors.lastname: Rathore
authors.affiliation: Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA.
authors.forename: Pammela
authors.initials: P
authors.lastname: Romo
authors.affiliation: Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA.
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Banyan Biomarkers, Inc, Alachua, FL, 32615, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hayes
authors.affiliation: University of Miami Leonard M. Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Wang
authors.affiliation: University of Miami Leonard M. Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: W Dalton
authors.initials: WD
authors.lastname: Dietrich
authors.affiliation: Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA. kwang@ufl.edu.|Physiological Sciences and Chemistry, University of Florida, Gainesville, FL, 32611, USA. kwang@ufl.edu.
authors.forename: Kevin K W
authors.initials: KKW
authors.lastname: Wang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D018836:Inflammation Mediators; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; C051774:neurofilament protein H
keywords: Biomarkers; Glial injury; Neuronal injury; Spinal cord injury; Systems biology