Elevated Atherosclerotic Biomarkers In Mice With Mild Blast Traumatic Brain Injury And Chronic Variable Stress

Introduction: Traumatic brain injury (TBI) and stress are significant health concerns that have atherosclerotic cardiovascular disease (ASCVD) effects. Stress and injury can elevate neurochemicals and hormones in the brain that lead to dysfunction of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system increasing inflammation, which plays a role in the development of ASCVD. Animal models can provide a method of separating mild TBI (mTBI) from models of chronic stress. Hypothesis: We hypothesize that mild blast TBI (mbTBI) and chronic variable stress (CVS) will result in elevated ASCVD biomarkers in mice. Methods: Frozen hearts from C57BL/6J mice (8 weeks, N=16, 8 male/8 randomly cycling female) were obtained through an IACUC approved study. The C57BL/6J mice were part of a mild blast TBI (mbTBI) study utilizing a blast chamber to receive a short duration shock wave (<10 msec, mean peak pressure of blast waves 19.9 psi). A group was subjected to CVS for two weeks prior to the blast, plus one week after blast. All groups were followed for four weeks. Western Blots with relative expression (normalized) were performed using an infrared imaging system. ERK1, ERK2, Galactein 3, Endothelin-1, BDNF, NT-Pro-BNP, and NRG1. ANOVA with Tukey HSD correction and descriptive statistics were performed using SPSS with significance by α of 0.05. Results: ERK1: mbTBI and CVS (p<0.05). CVS +mbTBI to CVS (0.015)( p<0.05 ), compared to mbTBI (0.017). ERK2: mbTBI sham = 0.009, CVS only = 0.008, mbTBI only = 0.008 and CVS + mbTBI = 0.012. Galectin-3 (Gal-3): CVS only = 0.144, CVS+mbTBI = 0.168, mbTBI (0.114) to sham (0.111) ( p<0.05 ). NT-Pro-BNP: CVS+mbTBI = 0.168, sham 0.076. mbTBI alone (0.077) and CVS alone (0.078). NRG1: mbTBI (0.195) and mbTBI with CVS (0.178). CVS only group (0.157). ET-1: mbTBI sham = 0.068, CVS only = 0.080 mbTBI only = 0.084 and CVS+mbTBI = 0.134. BDNF: CVS only = 0.053, CVS+mbTBI = 0.069. Sham group (0.047), mbTBI (0.038). Conclusion: Our results on proteins related to a broad spectrum of vascular growth, innervation, function, inflammation and markers of atherosclerotic plaque development suggest that mbTBI and/or chronic stress may increase risk for developing early ASCVD.