The main goal of this core is to identify a panel of surrogate protein markers measurable in human serum that,in combination with other clinical factors, predicts long-term dysfunction following mild TBI. A second goal is touse surrogate markers for axonal degeneration to promote studies of the underlying molecular mechanisms andprovide further validation for experimental models used in this proposal. Thus far, no individual marker hasconsistently demonstrated the ability to predict long-term functional impairment following mild TBI. To identifynew markers for TBI and develop a marker panel, my laboratory initiated the first global analysis of proteinrelease from degenerating neurons. We identified 14-3-3(3, 14-3-3^, a hypophpsphorylated form ofneurofilament H, a calpain-derived cleavage product of a-spectrin, and a caspase cleavage product of aspectrinas highly abundant neuron-enriched proteins released from dying neurons. The validity of thisapproach was established by immunodetection of these proteins in CSF and serum following TBI or cerebralischemia in rats, as well as severe TBI or surgically-induced circulation arrest in humans. To extend thisresearch to mild human TBI, the specific aims of the core are to: (1) determine relationships between surrogatemarker protein release, sodium channel dysfunction and axonal degeneration in a neuronal culture model foraxonal injury (Project 3); (2) analyze our novel surrogate marker panel in a pig model of mild TBI, and relatechanges to axonal histopathology and sodium channel dysfunction (Project 2); (3) evaluate serum elevations forthe same marker panel in mild human TBI, and compare their levels with cognitive, neurological, andradiological measures of dysfunction (Project 1). A surrogate marker-based method for the prognosis of mildTBI, along with a simple quantitative means of assessing experimental neuroprotective therapies, would haveenormous benefit for the management and treatment of mild TBI.
| Chen, H Isaac; Wolf, John A; Smith, Douglas H (2017) Multichannel activity propagation across an engineered axon network. J Neural Eng 14:026016 |
| Smith, Douglas H; Stewart, William (2016) Tackling concussion, beyond Hollywood. Lancet Neurol 15:662-663 |
| Stewart, William; Smith, Douglas H (2016) Time to be blunt about blast traumatic brain injury. Lancet Neurol 15:896-898 |
| 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 |
| 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 |
| Hay, Jennifer; Johnson, Victoria E; Smith, Douglas H et al. (2016) Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury. Annu Rev Pathol 11:21-45 |
| 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 |
| 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 |
| Levin, Harvey S; Diaz-Arrastia, Ramon R (2015) Diagnosis, prognosis, and clinical management of mild traumatic brain injury. Lancet Neurol 14:506-17 |
| 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 |
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