title: Behavioral, blood, and magnetic resonance imaging biomarkers of experimental mild traumatic brain injury.
abstract: Repeated mild traumatic brain injuries (mTBI) may lead to serious neurological consequences, especially if re-injury occurs within the period of increased cerebral vulnerability (ICV) triggered by the initial insult. MRI and blood proteomics might provide objective measures of pathophysiological changes in mTBI, and indicate when the brain is no longer in a state of ICV. This study assessed behavioral, MRI, and blood-based markers in a rat model of mTBI. Rats were given a sham or mild fluid percussion injury (mFPI), and behavioral testing, MRI, and blood collections were conducted up to 30 days post-injury. There were cognitive impairments for three days post-mFPI, before normalizing by day 5 post-injury. In contrast, advanced MRI (i.e., tractography) and blood proteomics (i.e., vascular endothelial growth factor) detected a number of abnormalities, some of which were still present 30 days post-mFPI. These findings suggest that MRI and blood proteomics are sensitive measures of the molecular and subtle structural changes following mTBI. Of particular significance, this study identified novel tractography measures that are able to detect mTBI and may be more sensitive than traditional diffusion-tensor measures. Furthermore, the blood and MRI findings may have important implications in understanding ICV and are translatable to the clinical setting.
authors.affiliation: Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, 3010, Australia.|The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3052, Australia.
authors.forename: David K
authors.initials: DK
authors.lastname: Wright
authors.affiliation: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, 3050, Australia.
authors.forename: Jack
authors.initials: J
authors.lastname: Trezise
authors.affiliation: Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
authors.forename: Alaa
authors.initials: A
authors.lastname: Kamnaksh
authors.affiliation: Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
authors.forename: Ramsey
authors.initials: R
authors.lastname: Bekdash
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3052, Australia.|Department of Electrical and Electronic Engineering, The University of Melbourne, Parkville, VIC, 3010, Australia.
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Johnston
authors.affiliation: Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, 3010, Australia.
authors.forename: Roger
authors.initials: R
authors.lastname: Ordidge
authors.affiliation: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, 3050, Australia.
authors.forename: Bridgette D
authors.initials: BD
authors.lastname: Semple
authors.affiliation: Centre for Stroke and Brain Injury, School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW, 2308, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gardner
authors.affiliation: School of Health Sciences, The University of Newcastle, Callaghan, NSW, 2308, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Stanwell
authors.affiliation: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, 3050, Australia.
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
authors.affiliation: Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
authors.forename: Denes V
authors.initials: DV
authors.lastname: Agoston
authors.affiliation: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, 3050, Australia.
authors.forename: Sandy R
authors.initials: SR
authors.lastname: Shultz
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D000070642:Brain Injuries, Traumatic / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D015415:Biomarkers; D001798:Blood Proteins