Infection Hinders Blood Vessel Repair after TBI

Viral Infection Slows Blood Vessel Repair After TBI: Seven days after mTBI, the blood vessels (stained in red) in the tissues around the brain are not completely repaired. A marker for intact vessels was used (labeled in green) to distinguish fully functional blood vessels (yellow) from ones that are still damaged (red).

Photo:  McGavern Lab, NINDS

Traumatic brain injury (TBI) and other injuries to blood vessels in the brain, like stroke, are a leading cause of long-term disability or death. NINDS researchers have found a possible explanation for why some patients recover much more poorly from brain injury if they later become infected. The findings were published in Nature Immunology.

Using a previously developed mouse model for mild TBI (mTBI), the research team discovered that viral, fungal or a mimic for bacterial infections all affected blood vessel repair within the meninges, the protective covering of the brain. Looking closer, they observed that some cells of the immune system no longer moved into the site of the injury, which occurred in the uninfected animals, suggesting they were responding to systemic infection. The study also looked in a second injury model called a cerebrovascular injury (CVI) and saw a similar effect on repair.

Normally, the immune system would fight off infection over repair, said NINDS scientist Dr. Dorian McGavern. “Because the body is dealing with a greater threat, cells that would normally repair the damaged blood vessels in or around the brain are needed elsewhere.” 

This change in priority for the immune system is not permanent, as infected mice were able to eventually repair the blood vessel damage later compared to uninfected mice, unless a second infection was encountered. This timing is especially critical in the case of CVI mice, because the delay in response produced by infection led to permanent cognitive dysfunction and damage to the brain tissue. The repaired brain blood vessels, which are normally very well sealed, remained permanently leaky.

Systemic infections are common among patients hospitalized for TBI and CVI, and they have been linked to poorer outcomes.

“The presence of infection causes the immune system to take a break from repair while it fights off the virus,” said McGavern. “In the case of mild TBI, this seems to be ok, but when you have a large vascular injury in the brain itself, like a stroke, every minute counts.”