Every year in the United States over one million individuals sustain a concussion, with over 300,000 of these injuries occurring during sports participation. Concussion diagnosis and management represent major clinical challenges. A significant number of concussion patients go on to experience persistent dysfunction. With no objective marker of concussion-related neuropathology, it is challenging, if not impossible to predict who will fall into this prolonged recovery group. We hypothesize that persisting concussion symptoms are a result of trauma-induced neuronal injury. Blood markers of the biochemical signaling pathways underlying neuronal degeneration offer a promising marker of the presence and extent of this damage. The proposed project is designed to evaluate neuronal damage as a cause of persisting concussion symptoms. Our method represents an innovation over previous biomarker research in this population, in that the proposed panel assays mechanism-based markers informed by the study of protein release from degenerating cultured neurons. Our panel includes a hypophosphorylated form of neurofilament H (pNFH), calpain-cleaved - spectrin, and caspase-cleaved -spectrin. Specifically, we will measure serum levels of these proteins in concussed athletes, and evaluate their relationship to cognitive dysfunction. To accomplish this, we will collect samples from collegiate athletes 6, 24, 48, and 96 hours after injury. Sensitivity will be established by comparing serum biomarker concentrations in concussed athletes with those from uninjured age and sex matched control participants from the same athletic teams. Prognostic utility will be evaluated by correlating biomarker concentrations with cognitive test performance at 48 hours and 3 weeks post-injury. The success of this project would provide support for an objective, minimally invasive marker of concussion-related neuropathology, and mark a critical step towards identification and treatment of patients at risk for persistent cognitive dysfunction. This fellowship will not only contribute needed information to the field, but will also uniquely qualify the applicant to embark on research career as a translational clinical neuropsychologist with expertise in both behavioral and biochemical measures of brain function.

Public Health Relevance

Every year in the United States over one million individuals suffer from a concussion. Many will go on to experience persistent dysfunction; yet, remarkably, there is no objective measure of concussion pathophysiology and no validated predictor of its course. There is an urgent public health need for an objective non-invasive marker of the presence and extent of concussion-related neuropathology in order to improve clinical management of these injuries.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F01-F (20))
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Bellgowan, Patrick S F
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University of Pennsylvania
Schools of Medicine
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Rabinowitz, Amanda R; Levin, Harvey S (2014) Cognitive sequelae of traumatic brain injury. Psychiatr Clin North Am 37:1-11