Open AccessEnoxaparin Attenuates Acute Lung Injury and Inflammasome Activation after Traumatic Brain Injury
Author(s) -
Nadine Kerr,
Juan Pablo de Rivero Vaccari,
Cailey Weaver,
W. Dalton Dietrich,
Tahir Ahmed,
Robert W. Keane
Publication year - 2021
Publication title -
journal of neurotrauma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.653
H-Index - 149
eISSN - 1557-9042
pISSN - 0897-7151
DOI - 10.1089/neu.2020.7257
Subject(s) - ards , inflammasome , medicine , traumatic brain injury , lung , inflammation , anesthesia , pathology , pharmacology , immunology , psychiatry
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 of enoxaparin 30 min after injury. Lung and brain tissue were collected 24 h post-TBI and were analyzed by immunoblotting for expression of the inflammasome proteins, caspase-1 and interleukin (IL)-1β. 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-1β in the brain and lungs of mice after injury. Treatment with enoxaparin attenuated inflammasome expression in the brain and lungs 24 h after injury. Enoxaparin significantly decreased ALI score as well as neutrophil and macrophage infiltration in lungs at 24 h 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 after TBI may have therapeutic potential.