About 300,000 people are hospitalized for traumatic brain injury (TBI) each year. After TBI,
secondary brain injury escalates due in part to heightened levels of oxidant injury,
inflammation, and vascular injury. Traumatic cerebral vascular injury (TCVI) may begin almost
immediately after the primary injury and evolve into chronic neurodegenerative conditions.
TCVI is a very complex TBI endophenotype and microvascular injuries have been described in a
plethora of animal and human TBI studies. These injuries consist of endothelial injury,
disruption of the blood brain barrier (BBB), a reduction of capillary density, intravascular
microthrombi, and white-matter degeneration. Recently, use of magnetic resonance imaging
(MRI)-Blood Oxygen Level Dependent (BOLD) combined with hypercapnia (high spatial and
temporal resolution) by our research group has proven to be more sensitive at measuring
alterations of cerebral blood flow (CBF) in TBI subjects. The goal of the proposed research
is to test the efficacy of Viagra® (sildenafil) at normalizing CBF and improving cognitive
outcomes in people that have experienced a TBI. Sildenafil is a phosphodiesterase-5 (PDE-5)
inhibitor that has previously been administered as a therapy for high blood pressure and
erectile dysfunction. In people that have been affected by stroke-induce neurotrauma,
sildenafil improved CBF and was found to be neuroprotective. With respect to chronic TBI,
previous studies have demonstrated that sildenafil therapy potentiates cardiovascular
reactivity (CVR) in areas of the brain with damaged endothelium. In this proposal, the
investigators will test the hypothesis that sildenafil treatment in boxers/Mixed Martial Arts
(MMA) fighters soon after concussion normalizes CBF, potentiates CVR, reduces post-concussion
symptoms, and improves cognition.