title: Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats.
abstract: Traumatic brain injury (TBI) represents a critical health problem of which diagnosis, management, and treatment remain challenging. TBI is a contributing factor in approximately one-third of all injury-related deaths in the United States. The Centers for Disease Control and Prevention estimate that 1.7 million people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics-systems biology is proving to be a prominent tool in biomarker discovery for central nervous system injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI) model of experimental TBI in rat model to assess the temporal-global proteome changes after acute (1 day) and for the first time, subacute (7 days), post-injury time frame using the established cation-anion exchange chromatography-1D SDS gel electrophoresis LC-MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entity, we usedin silicosystems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1 day) and subacute (7 days) periods post-TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7 days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is among the first to assess temporal neuroproteome changes in the CCI model. Data presented here unveil potential neural biomarkers and therapeutic targets that could be used for diagnosis, for treatment and, most importantly, for temporal prognostic assessment following brain injury. Of interest, this work relies onin silicobioinformatics approach to draw its conclusion; further work is conducted for functional studies to validate and confirm the omics data obtained.
authors.affiliation: Program for Neurotrauma, Neuroproteomics and Biomarkers Research, Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Program for Neurotrauma, Neuroproteomics and Biomarkers Research, Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Firas H
authors.initials: FH
authors.lastname: Kobeissy
authors.affiliation: Center of Innovative Research, Banyan Biomarkers Inc. , Alachua, FL , USA.
authors.forename: Joy D
authors.initials: JD
authors.lastname: Guingab-Cagmat
authors.affiliation: Program for Neurotrauma, Neuroproteomics and Biomarkers Research, Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Program for Neurotrauma, Neuroproteomics and Biomarkers Research, Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Program for Neurotrauma, Neuroproteomics and Biomarkers Research, Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Program for Neurotrauma, Neuroproteomics and Biomarkers Research, Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Moghieb
authors.affiliation: Department of Neurosurgery, Virginia Commonwealth University School of Medicine , Richmond, VA , USA.
authors.forename: Olena Y
authors.initials: OY
authors.lastname: Glushakova
authors.affiliation: Department of Neurosciences, University of Messina , Messina , Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mondello
authors.affiliation: Brain Trauma Neuroprotection and Neurorestoration Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research , Silver Spring, MD , USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Boutté
authors.affiliation: NeuroTheranostics Inc., Detroit, MI, USA; Henry Ford Health System, Detroit, MI, USA.
authors.forename: John
authors.initials: J
authors.lastname: Anagli
authors.affiliation: Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY, USA; Department of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Rubenstein
authors.affiliation: Faculty of Medicine, Beirut Arab University, Beirut, Lebanon; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Hisham
authors.initials: H
authors.lastname: Bahmad
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Wagner
authors.affiliation: Program for Neurotrauma, Neuroproteomics and Biomarkers Research, Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Program for Neurotrauma, Neuroproteomics and Biomarkers Research, Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Department of Neurosurgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hayes
authors.affiliation: Program for Neurotrauma, Neuroproteomics and Biomarkers Research, Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Program for Neurotrauma, Neuroproteomics and Biomarkers Research, Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
keywords: biomarker; controlled cortical impact; inflammation; oxidative stress; prognosis and therapeutics; proteomics; traumatic brain injury