Acute lung injury (ALI) and cardiac dysfunction are common in traumatic brain injury (TBI) patients and always indicate poor outcomes. Inflammatory responses play important roles in TBI-induced cardiac and pulmonary damage. Fingolimod, an immunomodulatory agent, alleviates brain edema, restores the integrity of the blood–brain barrier (BBB), and improves functional deficits by inhibiting multiple inflammatory responses. Fingolimod (1 mg/kg) was injected intraperitoneally at 2 h after the controlled cortical impact (CCI) model was established in adult male mice. The concentration of inflammatory cytokines in the lung and heart after TBI was measured with a cytokine array. The lung wet/dry weight ratio and Evans blue dye leakage were used to quantify pulmonary edema and capillary leakage. Immunofluorescence, electron microscopy, and echocardiographic examination were used to assess the pathology and functional deficits in hearts. We found that TBI caused significant heart and lung damage. The administration of fingolimod significantly reduced the elevated inflammatory cytokine production, neutrophil infiltration, the leakage of protein in bronchoalveolar lavage fluid (BALF), and the wet/dry weight ratio in lung tissue at 3 days after TBI. In addition, fingolimod treatment also alleviated the inflammatory response in the heart; decreased cardiac apoptosis, fibrosis, and histological microstructural changes; and improved cardiac function from 3 days after TBI and maintained it for 30 days after TBI as measured by echocardiography. These results suggest that TBI resulted in significant cardiac and pulmonary damage accompanied by significant inflammatory responses in heart and lung tissue. Fingolimod treatment reduced the inflammatory response and alleviated TBI-induced lung and heart injury.

中文翻译：

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芬戈莫德减轻创伤性脑损伤后的肺损伤和心脏功能障碍。

急性肺损伤 (ALI) 和心功能不全在创伤性脑损伤 (TBI) 患者中很常见，并且总是表明预后不佳。炎症反应在 TBI 引起的心脏和肺损伤中起重要作用。芬戈莫德是一种免疫调节剂，可减轻脑水肿，恢复血脑屏障 (BBB) 的完整性，并通过抑制多种炎症反应来改善功能缺陷。在成年雄性小鼠中建立受控皮质影响 (CCI) 模型后 2 小时腹腔注射芬戈莫德 (1 mg/kg)。用细胞因子阵列测量 TBI 后肺和心脏中炎性细胞因子的浓度。肺湿/干重量比和伊文思蓝染料渗漏用于量化肺水肿和毛细血管渗漏。免疫荧光、电子显微镜、和超声心动图检查用于评估心脏的病理和功能缺陷。我们发现 TBI 会造成严重的心脏和肺损伤。芬戈莫德的给药显着降低了 TBI 后 3 天升高的炎性细胞因子产生、中性粒细胞浸润、支气管肺泡灌洗液 (BALF) 中的蛋白质渗漏以及肺组织的湿/干重量比。此外，芬戈莫德治疗也减轻了心脏的炎症反应；减少心脏细胞凋亡、纤维化和组织学微观结构变化；并且从 TBI 后 3 天开始改善心脏功能，并在 TBI 后通过超声心动图测量维持 30 天。这些结果表明，TBI 导致显着的心脏和肺损伤，伴随着心脏和肺组织的显着炎症反应。芬戈莫德治疗降低了炎症反应并减轻了 TBI 引起的肺和心脏损伤。