PROJECT SUMMARY/ABSTRACT
Subconcussive head impacts (SHI), defined as a head impact without overt symptoms of concussion, are
incredibly common among soccer players as a result of soccer heading. SHI from repetitive soccer headings
may pose a risk of triggering neurodegenerative disorders later in life. However, despite the popularity of soccer
with nearly 24 million people in the U.S. across all ages and sexes playing soccer, there is currently no
prophylactic intervention to mitigate or ameliorate neurologic stress from soccer heading. Our data suggest at
least 4 neurologic features related to subconcussive brain injury. For example, acute SHI from soccer headings
and football tackles lead to elevation of neural injury blood biomarkers (NF-L, GFAP, tau, UCH-L1, S100B),
changes in axonal microstructural integrity, and sympathetic hyperreactivity, triggering hypertensive
characteristic, and neuro-ophthalmologic impairments, such as convergence and saccades. Growing data from
many preclinical and clinical studies suggest that these cellular and physiologic alterations may be preventable
by pretreatment with omega-3 fatty acids (FA), especially with docosahexaenoic acid (DHA) and
eicosapentaenoic acid (EPA), which has shown to alleviate neuronal and glial oxidation and calcium triggered
excitotoxicity, mitigate elevations of plasma NF-L levels (axonal injury marker), and maintain cognitive function
after various severities of traumatic brain injury (TBI). We propose a randomized controlled trial to obtain
mechanistic insights into the biophysiologic interaction between DHA+EPA pretreatment and acute SHI and
determine whether, and to what extent, pretreatment with DHA and EPA combined is neuroprotective against
repetitive SHI. Our central hypothesis is that DHA+EPA pretreatment will be neuroprotective against SHI.
We hypothesize that 20 controlled acute soccer headings will result in microdamage to neuronal structures and
sympathetic hyperreactivity, but that 8 weeks of pretreatment with 3.4 g/d DHA+EPA will significantly prevent
such alterations. There are three synergistic aims. We hypothesize that (1) DHA+EPA will prevent neuronal and
astrocyte damage after acute and cumulative SHI, as assessed by the panel of blood biomarkers (NF-L, tau,
GFAP, UCH-L1, S100B); (2) DHA+EPA pretreatment will attenuate disruption in axonal microstructure and
altered functional connectivity after acute and cumulative soccer headings; and (3) DHA+EPA pretreatment will
prevent the triggering of sympathetic hyperreactivity after soccer headings, as reflected by a typical
cardiovascular response to the cold pressor test. If our hypotheses are confirmed, our findings will provide a
means to intervene in the SHI-induced neurological damage that can be monitored through multimodal
neurologic assessments. Clinical implications of the study translate beyond soccer to the public at large.
