Sunday, May 18, 2025
5/18/2025
Subconcussive neurodegenerative progression in adolescent athletes - PROJECT SUMMARY/ABSTRACT Every year, nearly 2.5 million U.S. high school athletes participate in contact sports. Each of these athletes sustains an average of 650 subconcussive head impacts (SHI) in a single season, with some athletes exceeding 1,000 hits from, for example, football tackles and soccer headings. A subconcussive head impact is defined as an impact that does not trigger the clinically detectable signs and symptoms of concussion. However, these mechanical forces, if applied repeatedly, can trigger subclinical cellular and molecular disruptions in brain cells. Adolescence is an especially vulnerable time for neurodevelopment, because of (a) arborization of white matter tracts within the prefrontal cortex (PFC) and between the PFC and limbic structures and (b) synaptic pruning. Our clinical studies suggest that both acute and chronic exposure to SHI can impair neuro-ophthalmologic functions, increase the levels of brain-derived proteomic (NF-L, Tau, UCH-L1, GFAP, S100B) and exosome (7 neuron/glia-specific exosomes) biomarkers in blood, and trigger changes in the microstructural integrity of white matter. Despite these serious public health implications, no empirical basis exists for establishing a safety protocol or predicting who may develop cumulative pathologic sequelae from SHI, and to what extent, during a 4-year high school football career. The overall goal of this study is to determine the longitudinal effects of SHI on neural integrity and function in adolescents throughout their high school football careers and to identify the dose and intensity of SHI that induce chronic, progressive neurodegeneration. Our central hypothesis is that SHIs in adolescents will gradually degrade neuronal cellular and functional integrity across multiple football seasons in a head-impact-dependent manner. There are three related, hypothesis-driven aims. We hypothesize (1) that a panel of brain-derived proteomic (NF-L, Tau, UCH-L1, GFAP) and exosome markers will increase in blood in response to SHI; (2) that chronic exposure to SHI will disrupt neuro-ophthalmologic function, as reflected in increased variability in smooth eye pursuit and slower King-Devick performance; and (3) that repetitive SHI will lead to disruption in white matter microstructure and changes in resting-state fMRI connectivity. We further hypothesize that with repetitive SHI these changes may not return to baseline and may carry over and accumulate from one season to the next. By tracking SHI exposure and neurologic health in the same athletes for 4 years, the proposed study will help to establish safety guidelines for adolescent athletes. The long-term goal is to prevent neurocognitive deficits in competitive sports athletes.
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