Researchers Look for Brain Injury Link That Damages Lungs

Randy Rozek • September 10, 2014

Following a brain injury, there’s an inflammatory cascade with a molecule named HMGB1, which releases into the blood after a brain injury. When HMGB1 reaches the lung, it attaches to a receptor called RAGE. Dr. Weber, one of the IU researchers for this phenomena, has said that the lungs are abundant with RAGE receptors, so they have increased vulnerability to the inflammatory process of TBI.

IU researchers have wanted to understand how TBI is associated with lung injuries during the inflammatory situation that becomes active in the lungs. During the process, they determined that the most likely candidates were HMGB1 and the RAGE pathway. When researchers genetically eliminated RAGE receptors from mice and gave them a controlled TBI, the mice without RAGE receptors did not show signs of lung injury. However, the mice with RAGE receptors showed increased levels of HMGB1 and lung injury from inflammation.

During the experiment, Dr. Wilkes, collaborating with IU Health Lung Transplant Program, had a collection of tissue samples and blood from donors who gave a lung transplant. When reviewing the samples and patient outcomes, they discovered that an increased HMBG1 level in donors had a poor short-term outcome for transplant recipients.

Fluid leakage in the lungs can show clear signs, even four hours after head injuries. Researchers feel optimistic that this research will become a therapeutic target for those suffering from lung impairment due to TBI. With this research, a scarce donor pool for lungs may expand and outcomes could improve.

Clinical evidence shows that transplants due to a TBI are not as successful for recipients due to impaired brain function. This research could help that problem. Considering that only 15 to 20 percent of lungs evaluated are approved for transplant, there is an opportunity to help those suffering from traumatic brain injuries.