Fingolimod Attenuates Lung Injury and Cardiac Dysfunction after Traumatic Brain Injury

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.