Enoxaparin Attenuates Acute Lung Injury and Inflammasome Activation Following Traumatic Brain Injury.

Traumatic Brain injury (TBI) patients frequently develop cardiopulmonary system complications such as Acute Lung Injury (ALI) /Acute Respiratory Distress Syndrome (ARDS). However, the mechanism by which TBI causes ALI/ARDS is not fully understood. Here we used a severe TBI model to examine the effects of a low-molecular-weight heparin, Enoxaparin on inflammasome activation and lung injury damage. We investigated whether Enoxaparin inhibits ALI and inflammasome signaling protein expression in the brain and lungs after TBI in mice. C57/BL6 mice were subjected to severe TBI and were treated with vehicle or 1 mg/kg Enoxaparin 30 minutes after injury. Lung and brain tissue were collected 24 hours post-TBI and were analyzed by immunoblotting for the expression of the inflammasome proteins caspase-1 and IL-1. In addition, lung tissue was collected for histological analysis to determine ALI scoring and neutrophil and macrophage infiltration post-injury. Our data show that severe TBI induces increased expression of inflammasome proteins caspase-1 and IL-1 in the brain and lungs of mice after injury. Treatment with enoxaparin attenuated inflammasome expression in the brain and lungs 24 hours after injury. Enoxaparin significantly decreased the ALI score as well as neutrophil and macrophage infiltration in the lungs at 24 hours after injury. This study demonstrates that Enoxaparin attenuates ALI and inhibits inflammasome expression in the brain and lungs after TBI. These findings support the hypothesis that inhibition of the neural-respiratory inflammasome axis that is activated following TBI may have therapeutic potential.