BACKGROUND AND PURPOSE Intracerebral hemorrhage (ICH) patients frequently encounter cardiovascular complications which may contribute to increased mortality and poor long term outcome. ICH induces systemic oxidative stress and activates peripheral immune responses which are involved in the pathological cascade leading to cardiac dysfunction and heart failure after ICH. We have previously reported that ICH induces progressive cardiac dysfunction in mice without primary cardiac diseases. In this study, we have investigated the role of immune response in mediating cardiac dysfunction post ICH in mice. METHODS Adult male C57BL/6 J mice were randomly assigned to the following groups (n = 8/group): 1) sham control; 2) ICH; 3) splenectomy with ICH (ICH + Spx); 4) splenectomy alone (Spx). Echocardiography was performed at 7 and 28 days after ICH. A battery of neurological and cognitive tests were performed. Flow cytometry, western blot and immunostaining were used to test mechanisms of ICH induced cardiac dysfunction. RESULTS Compared to sham control mice, Spx alone does not induce acute (7 day) or chronic (28 day) cardiac dysfunction. ICH induces significant neurological and cognitive deficits, as well as acute and chronic cardiac dysfunction compared to sham control mice. Mice subjected to ICH + Spx exhibit significantly improved neurological and cognitive function compared to ICH mice. Mice with ICH + Spx also exhibit significantly improved acute and chronic cardiac function compared to ICH mice indicated by increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), decreased cardiac fibrosis, decreased cardiomyocyte hypertrophy, decreased cardiac infiltration of immune cells and decreased expression of inflammatory factor and oxidative stress in the heart. CONCLUSIONS Our study demonstrates that splenectomy attenuates ICH-induced neurological and cognitive impairment as well as ICH-induced cardiac dysfunction in mice. Inflammatory cell infiltration into heart and immune responses mediated by the spleen may contribute to ICH-induce acute and chronic cardiac dysfunction and pathological cardiac remodeling.

中文翻译：

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脑出血后，脾脏相关的免疫反应介导脑心相互作用。

背景和目的脑出血（ICH）患者经常遇到心血管并发症，这可能导致死亡率增加和长期预后不良。ICH诱发全身性氧化应激并激活周围免疫应答，这些免疫应答与导致ICH后心脏功能障碍和心力衰竭的病理级联有关。我们以前曾报道过，ICH可在无原发性心脏病的小鼠中诱发进行性心脏功能障碍。在这项研究中，我们研究了免疫应答在介导ICH后介导心脏功能障碍中的作用。方法成年雄性C57BL / 6 J小鼠随机分为以下各组（每组8只）：1）假对照组； 1）假对照组。2）ICH；3）ICH脾切除术（ICH + Spx）；4）单独行脾切除术（Spx）。ICH后7天和28天进行超声心动图检查。进行了一系列的神经和认知测试。流式细胞仪，免疫印迹和免疫染色被用来测试ICH引起的心脏功能障碍的机制。结果与假对照组相比，单独的Spx不会诱发急性（7天）或慢性（28天）心脏功能障碍。与假对照小鼠相比，ICH会引起严重的神经和认知功能障碍，以及急性和慢性心脏功能障碍。与ICH小鼠相比，接受ICH + Spx的小鼠表现出明显改善的神经和认知功能。与ICH小鼠相比，ICH + Spx小鼠还表现出显着改善的急性和慢性心脏功能，其表现为左心室射血分数（LVEF）和左心室分数缩短（LVFS）增加，心脏纤维化减少，心肌细胞肥大减少，减少免疫细胞的心脏浸润，降低心脏中炎症因子和氧化应激的表达。结论我们的研究表明，脾切除术可减轻小鼠ICH引起的神经和认知功能障碍以及ICH引起的心脏功能障碍。炎性细胞渗入心脏和脾脏介导的免疫反应可能导致ICH引起急性和慢性心脏功能障碍和病理性心脏重塑。