ABSTRACT
Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.
ABSTRACT
Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.
ABSTRACT
<p><b>AIM</b>Through studying local regulatory mechanisms in pulmonary arteries (PA) and thoracic aortae (TA) under simulated microgravity (SM), to collect some data for the researches of adaptive mechanisms in pulmonary and systemic arteries and for the mechanisms accounting for orthostatic intolerance after SM.</p><p><b>METHODS</b>Cardiopulmonary circulatory function during 7-day 6 degrees head down bed rest (HDT) in male young volunteers was measured with a XXH-2000 pulmonary circulation and cardiac function instrument. - 30 degrees C tail suspended (TS) rats were used as the model to simulate the physiological effects of M. The PA and TA changes of vasoreactivity were respectively observed by vitro vessel rings perfusion.</p><p><b>RESULTS</b>The changes in volume of PA and pulmonary vein during a cardiac cycle and the preload in left cardiac ventricle in men increased significantly in the initial HDT. The super-regulatory phenomena appeared in both pulmonary and systemic circulation, but earlier and more obviously in pulmonary circulation than systemic circulation during 96-144 h. The dilatory reactivity in TS7 PA increased significantly, tended to decrease in TS14. The dilatory reactivity of TA in TS7 had a significant increase, had a slight increase in TS14. The contractile reactivity of PA decreased slightly in TS7 from CON, and were attenuated significantly in TS14. The contractile reactivity of TA in TS14 decreased significantly. The responsiveness to KCl, phenylephrine and sodium nitroprusside in VEC- removed PA had no differences among all groups.</p><p><b>CONCLUSION</b>The differences in changes between pulmonary and systemic arteries under SM could be an important sign of depressed local regulatory function, which might be mainly due to dilatory function in VEC and contribute to the occurrence of orthostatic intolerance after SM.</p>