Traumatic brain injury (TBI) is a leading cause of death and disability in adolescents and young adults and therefore represents a major health problem. Although mild traumatic brain injury (MTBI) is generally nonfatal in this age range, the neurobehavioral effects can persist for months and their mediation by changes in the brain is poorly understood. To gain understanding of changes in brain imaging and neurobehavioral function over three months post-MTBI relative to orthopedic injury (Ol), Aim 1 addresses changes in the integrity of cerebral white matter as measured by diffusion tensor imaging (DTI), hemorrhagic lesions seen on susceptibility weighted imaging, and the magnetization transfer ratio on magnetization transfer imaging.
Aim 1 also addresses changes in brain region volumes of white matter, gray matter, and cerebrospinal fluid by analysis of magnetic resonance imaging.
Aim 1 also investigates the relation of serum biomarkers of MTBI obtained from a blood draw at baseline to the brain imaging variables and whether the concentrations of these biomarkers differentiate MTBI and Ol groups.
Aim 2 measures change over three months post-injury in MTBI patients relative to the Ol group in information processing speed, working memory, episodic memory, and executive functions and the relation of changes in these cognitive domains to brain imaging findings and to functional outcome.
Aim 3 measures change over three months in post-concussion symptoms, posttraumatic stress symptoms, emotional status, functional status, and health-related quality of life (HRQL).
Aim 3 also studies change in cognitive post-concussion symptoms in relation to brain imaging variables and the relation of change in cognitive, emotional, and somatic post-concussion symptoms to functional outcome and HRQL. We propose a prospective, longitudinal study of 220 right-handed patients, age 14-30 years old, including 88 with MTBI, 44 patients with TBI associated with moderate impairment of consciousness, and 88 patients with Ol without brain insult. Selection criteria for the two TBI groups include computed tomography within 24 hours post-injury that shows no brain lesions. All groups would undergo a baseline assessment within 96 hours post-injury, including assessment of pre-injury status, brain imaging, blood draw for surrogate biomarkers, and neurobehavioral testing including cognition, post-concussion and posttraumatic stress symptoms, emotional status, functional status, and HRQL. Brain imaging would be repeated at three months post-injury, and neurobehavioral assessment would be repeated at both one and three months post-injury. Multivariate statistics and the general linear mixed model would be used to analyze the data. By helping to understand the relation of changes in brain imaging to neurobehavioral changes after MTBI in young persons, this study's findings may suggest ways to reduce morbidity and enhance outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS056202-05
Application #
8377468
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$358,098
Indirect Cost
$47,634
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Johnson, Victoria E; Stewart, William; Weber, Maura T et al. (2016) SNTF immunostaining reveals previously undetected axonal pathology in traumatic brain injury. Acta Neuropathol 131:115-35
Ali, Zarina S; Johnson, Victoria E; Stewart, William et al. (2016) Neuropathological Characteristics of Brachial Plexus Avulsion Injury With and Without Concomitant Spinal Cord Injury. J Neuropathol Exp Neurol 75:69-85
Wilde, Elisabeth A; Hunter, Jill V; Li, Xiaoqi et al. (2016) Chronic Effects of Boxing: Diffusion Tensor Imaging and Cognitive Findings. J Neurotrauma 33:672-80
Hay, Jennifer R; Johnson, Victoria E; Young, Adam M H et al. (2015) Blood-Brain Barrier Disruption Is an Early Event That May Persist for Many Years After Traumatic Brain Injury in Humans. J Neuropathol Exp Neurol 74:1147-57
Patel, Tapan P; Man, Karen; Firestein, Bonnie L et al. (2015) Automated quantification of neuronal networks and single-cell calcium dynamics using calcium imaging. J Neurosci Methods 243:26-38
Rabinowitz, Amanda R; Li, Xiaoqi; McCauley, Stephen R et al. (2015) Prevalence and Predictors of Poor Recovery from Mild Traumatic Brain Injury. J Neurotrauma 32:1488-96
Schmidt, Adam T; Li, Xiaoqi; Hanten, Gerri R et al. (2015) A Longitudinal Investigation of Sleep Quality in Adolescents and Young Adults After Mild Traumatic Brain Injury. Cogn Behav Neurol 28:53-62
Ahmadzadeh, Hossein; Smith, Douglas H; Shenoy, Vivek B (2015) Mechanical Effects of Dynamic Binding between Tau Proteins on Microtubules during Axonal Injury. Biophys J 109:2328-37
Levin, Harvey S; Diaz-Arrastia, Ramon R (2015) Diagnosis, prognosis, and clinical management of mild traumatic brain injury. Lancet Neurol 14:506-17
Siman, Robert; Shahim, Pashtun; Tegner, Yelverton et al. (2015) Serum SNTF Increases in Concussed Professional Ice Hockey Players and Relates to the Severity of Postconcussion Symptoms. J Neurotrauma 32:1294-300

Showing the most recent 10 out of 45 publications