Immune response mediates the cardiac damage after subarachnoid hemorrhage

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Experimental neurology


Cardiac dysfunction is a common adverse effect of subarachnoid hemorrhage (SAH). Autopsy of SAH patients shows immunocyte infiltration into the heart. In this study, a SAH model of endovascular perforation was performed in adult male mice in order to test whether SAH causes cardiac dysfunction in non-primary cardiac disease young adult male mice and whether immune response mediates SAH induced cardiac and neurological deficit. Splenectomy was performed on a subpopulation of mice one week prior to induction of the SAH. Neurological functional tests, transthoracic Doppler echocardiography, immunofluorescent staining, and flow cytometry were performed to investigate neurological and cardiac function and immune/inflammatory effects of SAH in mice with or without splenectomy. We found that SAH significantly induces ventricular fibrillation and cardiac dysfunction identified by significantly reduced left ventricular ejection fraction, left ventricular fractional shortening, decreased heart rate, as well as increased macrophage and neutrophil infiltration into heart and inflammatory factor expression in the heart compared to sham control mice. SAH also induces neurological deficit, increases astrocyte and microglial activity, and inflammatory cell infiltration into brain as well as up-regulates inflammatory factor expression in the brain tissue. Splenectomy not only significantly improves neurological function, but also reduces cardiac dysfunction compared to SAH alone mice. Splenectomy in SAH mice significantly reduces inflammatory cell infiltration, and decreases NADPH oxidase-2 and macrophage chemokine protein-1 expression in heart and brain when compared to non-splenectomy SAH mice. Our data suggest that, SAH induces acute cardiac dysfunction in non-primary cardiac disease mice. Secondary immune response may play an important role in mediating brain-heart damage after SAH.

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