Immune Response Mediates Cardiac Dysfunction After Traumatic Brain Injury

Objective: Cardiovascular complications are common after TBI and are associated with increased morbidity and mortality.In this study,we investigated the possible role of the immune system in mediating cardiac dysfunction post TBI in mice.Methods: Adult male C57BL/6J mice were subjected to a TBI model of controlled cortical impact(CCI)without(sham surgery)or with splenectomy.Splenectomy was performed immediately prior to induction of TBI.Cardiac function was measured using echocardiography prior to TBI,and at 3 days and 30 days after TBI.Neurological and cognitive functional tests were performed by investigators blinded to the experimental groups.Immunoresponses were measured by flow cytometry at 3 days after TBI.Heart tissue immunostaining for evaluation of apoptosis,oxidative stress,inflammatory factors and cardiac fibrosis was performed at 3 and 30 days after TBI.Results: TBI mice exhibited significant cardiac dysfunction identified by decreased left ventricular ejection fraction(LVEF)and fractional shortening(FS)acutely(3 days)and chronically(30 days)after TBI.In addition,these mice exhibited significantly increased cardiomyocyte apoptosis,inflammation and oxidative stress at 3 and 30 days post TBI,as well as cardiac hypertrophy and fibrosis,and ventricular dilatation at 30 days after TBI.TBI mice subjected to splenectomy showed significantly improved cardiac function,and significantly decreased cardiac fibrosis,oxidative stress,cardiomyocyte apoptosis,as well as decreased infiltration of immune cells and inflammatory factor expression in the heart compared to TBI control mice.TBI mice exhibited severe neurological and cognitive function deficits.However,splenectomy did not improve neurological and cognitive functional outcome after TBI compared with the TBI control group.Conclusions: TBI induces infiltration of immune cells and inflammatory factor expression in the heart as well as cardiac dysfunction.Splenectomy decreases heart inflammation and improves cardiac function after TBI.Immune response may contribute to TBI-induced cardiac dysfunction.