New research from the University of Miami Miller School of Medicine has revealed a direct connection between traumatic brain injury (TBI) and lung damage. Scientists led by Nadine Kerr, Ph.D., a research assistant professor of neurological surgery, have identified what they call the “brain-lung axis.” This pathway involves extracellular vesicles (EVs), which are small packages released by cells in response to brain trauma.
The study found that when the brain is injured, it releases EVs containing proteins and other molecules that travel through the bloodstream to distant organs such as the lungs. These EVs can trigger inflammation in lung tissue, leading to acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome (ARDS). Up to 30% of TBI patients develop serious lung problems, increasing their risk of death.
Dr. Kerr’s team analyzed blood samples from 21 severe TBI patients. They discovered that those who developed lung injury had higher levels of inflammatory proteins both in their blood and within EVs compared to patients without lung complications. Laboratory tests showed that these EVs could activate an inflammatory response in human lung cells and induce programmed cell death.
Further investigation explored whether enoxaparin, an FDA-approved anti-coagulant with anti-inflammatory properties, could interrupt this process. In mouse models of severe TBI, administering enoxaparin 30 minutes after injury significantly reduced inflammatory protein levels in both brain and lungs. The drug also helped preserve lung structure and decreased infiltration of inflammatory cells into the lungs.
Kristine O’Phelan, M.D., professor of neurology and chief of the Neurocritical Care Division at the Miller School, noted changes in clinical practice based on these findings. Enoxaparin was previously avoided for TBI patients due to bleeding risks but is now used by Dr. O’Phelan for preventing blood clots such as deep vein thrombosis and pulmonary embolism in acutely injured TBI patients. The new research suggests enoxaparin may also help prevent lung complications by blocking EV-mediated inflammation.
“It is exciting to consider that using enoxaparin for routine prevention of blood clot complications may also help our patients by preventing pulmonary complications as well,” said Dr. O’Phelan.
This work highlights a possible dual benefit for enoxaparin: reducing both clotting risks and inflammation-related lung damage following traumatic brain injuries.
