title: Proteomic analysis and brain-specific systems biology in a rodent model of penetrating ballistic-like brain injury.
abstract: Proteomics and systems biology have significantly contributed to biomarker discovery in the field of brain injury. This study utilized 2D-DIGE-PMF-MS as a preliminary screen to detect biomarkers in a rat model of penetrating ballistic-like brain injury (PBBI). Brain-specific systems biology analysis of brain tissue identified 386 proteins having a fold change of more than 2, of which 321 proteins were increased and 65 were decreased 24 h after PBBI compared to sham controls. The majority of upregulated proteins were cytoskeletal (10.5%), nucleic acid binding (9.3%), or kinases (8.9%). Most proteins were involved in protein metabolism (22.7%), signal transduction (20.4%), and development (9.6%). Pathway analysis indicated that these proteins were involved in neurite outgrowth and cell differentiation. Semiquantitative Western blotting of 6, 24, 48, and 72 h after PBBI indicated ubiquitin carboxyl-terminal hydrolase isozyme L1 (a proposed traumatic brain injury biomarker in human clinical trials), tyrosine hydroxylase, and syntaxin-6 were found to be consistently elevated in brain tissue and cerebral spinal fluid after PBBI compared to sham controls. Combining proteomics and brain-specific systems biology can define underlying mechanisms of traumatic brain injury and provide valuable information in biomarker discovery that, in turn, may lead to novel therapeutic targets.
authors.affiliation: Brain Trauma Neuroprotection and Neurorestoration Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Boutté
authors.forename: Changping
authors.initials: C
authors.lastname: Yao
authors.forename: Firas
authors.initials: F
authors.lastname: Kobeissy
authors.forename: Xi-Chun
authors.initials: XC
authors.lastname: May Lu
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Wang
authors.forename: Kara
authors.initials: K
authors.lastname: Schmid
authors.forename: Frank C
authors.initials: FC
authors.lastname: Tortella
authors.forename: Jitendra R
authors.initials: JR
authors.lastname: Dave
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000737:chemistry; D001923:Brain Chemistry; D030562:Databases, Protein; D004195:Disease Models, Animal; D020197:Head Injuries, Penetrating / Q000378:metabolism* / Q000473:pathology; D006651:Histocytochemistry; D008297:Male; D011506:Proteins / Q000032:analysis; D020543:Proteome / Q000032:analysis* / Q000737:chemistry; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D049490:Systems Biology / Q000379:methods
chemical_list: D015415:Biomarkers; D011506:Proteins; D020543:Proteome