Inflammatory Response and Immune Regulation in Brain-Heart Interaction after Stroke

Abstract

Cerebrocardiac syndrome (CCS) is one of the secondary myocardial injuries after stroke. Cerebrocardiac syndrome may result in a poor prognosis with high mortality. Understanding the mechanism of the brain-heart interaction may be crucial for clinical treatment of pathological changes in CCS. Accumulating evidence suggests that the inflammatory response is involved in the brain-heart interaction after stroke. Systemic inflammatory response syndrome (SIRS) evoked by stroke may injure myocardial cells directly, in which the interplay between inflammatory response, oxidative stress, cardiac sympathetic/parasympathetic dysfunction, and splenic immunoregulation may be also the key pathophysiology factor. This review article summarizes the current understanding of inflammatory response and immune regulation in brain-heart interaction after stroke.

Figure 1

Immune response and inflammation in brain-heart interaction. Local inflammation induces blood-brain barrier (BBB) disruption, oxidative stress, and autonomic hyperactivity. Local inflammation in the injured brain also infiltrates into the systemic circulation. Systemic inflammatory response syndrome (SIRS) injures myocardial cells directly, as well as the interplay between inflammatory response and oxidative stress, cardiac sympathetic/parasympathetic dysfunction, and splenic immunoregulation. Brain-derived microvesicles (MVs) enter into the systemic circulation and then interact with the peripheral immune system. MVs are also involved in thrombus formation. Stroke triggers oxidative stress, and NOX-2 and MCP-1 regulate the release of cytokines/chemokines. Both sympathetic nerve and HPA axis activation cause catecholamine surge. Catecholamines mediate the increase of inflammatory cytokines, as well as spleen atrophy. The spleen regulates the immune response by increasing circulating lymphocytes, cytokines, chemokines, and macrophage migration. SIRS: systemic inflammatory response syndrome; BBB: blood-brain barrier; MVs: microvesicles; SNS: sympathetic nervous system; PNS: parasympathetic nervous system; ROS: reactive oxygen species; NOX-2: nitric oxide-2; MCP-1: monocyte chemoattractant protein-1; HPA: hypothalamic-pituitary adrenal.