title: Temporal MRI characterization, neurobiochemical and neurobehavioral changes in a mouse repetitive concussive head injury model.
abstract: Single and repeated sports-related mild traumatic brain injury (mTBI), also referred to as concussion, can result in chronic post-concussive syndrome (PCS), neuropsychological and cognitive deficits, or chronic traumatic encephalopathy (CTE). However PCS is often difficult to diagnose using routine clinical, neuroimaging or laboratory evaluations, while CTE currently only can be definitively diagnosed postmortem. We sought to develop an animal model to simulate human repetitive concussive head injury for systematic study. In this study, mice received single or multiple head impacts by a stereotaxic impact device with a custom-made rubber tip-fitted impactor. Dynamic changes in MRI, neurobiochemical markers (Tau hyperphosphorylation and glia activation in brain tissues) and neurobehavioral functions such as anxiety, depression, motor function and cognitive function at various acute/subacute (1-7 day post-injury) and chronic (14-60 days post-injury) time points were examined. To explore the potential biomarkers of rCHI, serum levels of total Tau (T-Tau) and phosphorylated Tau (P-Tau) were also monitored at various time points. Our results show temporal dynamics of MRI consistent with structural perturbation in the acute phase and neurobiochemical changes (P-Tau and GFAP induction) in the subacute and chronic phase as well as development of chronic neurobehavioral changes, which resemble those observed in mTBI patients.
authors.affiliation: Program for Neurotrauma, Neuroproteomics &Biomarkers Research, Departments of Psychiatry &Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Yang
authors.affiliation: 1] Program for Neurotrauma, Neuroproteomics &Biomarkers Research, Departments of Psychiatry &Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA [2] School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Drake
authors.initials: D
authors.lastname: Morgan
authors.affiliation: 1] Program for Neurotrauma, Neuroproteomics &Biomarkers Research, Departments of Psychiatry &Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA [2] School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Pan
authors.affiliation: Program for Neurotrauma, Neuroproteomics &Biomarkers Research, Departments of Psychiatry &Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Lin
authors.affiliation: Program for Neurotrauma, Neuroproteomics &Biomarkers Research, Departments of Psychiatry &Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Strang
authors.affiliation: Program for Neurotrauma, Neuroproteomics &Biomarkers Research, Departments of Psychiatry &Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Tyler M
authors.initials: TM
authors.lastname: Selig
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Perez
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Febo
authors.affiliation: Department of Neurology, Box #1213, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
authors.forename: Binggong
authors.initials: B
authors.lastname: Chang
authors.affiliation: Department of Neurology, Box #1213, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Rubenstein
authors.affiliation: Program for Neurotrauma, Neuroproteomics &Biomarkers Research, Departments of Psychiatry &Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
mesh_terms: D000818:Animals; D020208:Brain Injury, Chronic / Q000378:metabolism / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL