Inflammatory responses mediate brain-heart interaction after ischemic stroke in adult mice

Stroke induces cardiac dysfunction which increases post stroke mortality and morbidity particularly in aging population. Here, we investigated the effects of inflammatory responses as underlying mediators of cardiac dysfunction after stroke in adult mice. Adult (eight-to-nine months) male C57BL/6 mice were subjected to photothrombotic stroke. To test whether immunoresponse to stroke leads to cardiac dysfunction, splenectomy was performed with stroke. Immunohistochemistry, flow cytometry, PCR, ELISA and echocardiography were performed. We found marginal cardiac dysfunction at acute phase and significant cardiac dysfunction at chronic phase of stroke as indicated by significant decrease of left ventricular ejection fraction (LVEF) and shortening fraction (LVSF). Stroke significantly increases macrophage infiltration into the heart and increases IL-1β, IL-6, MCP-1, TGF-β and macrophage-associated inflammatory cytokine levels in the heart as well as induces cardiac-fibrosis and hypertrophy. Splenectomy with stroke significantly reduces macrophage infiltration into heart, decreases inflammatory factor expression in the heart, decreases cardiac hypertrophy and fibrosis, as well as significantly improves cardiac function compared to non-splenectomized adult stroke mice. Therefore, cerebral ischemic stroke in adult mice induces chronic cardiac dysfunction and secondary immune response may contribute to post stroke cardiac dysfunction.