Blast mTBI is associated with impaired function of the glymphatic system. Sleep quality is also a factor–Interventions to improve sleep may help

Veterans

Jul 22

By Kaori Hirano. This article was initially published in the 6/27/24 edition of our Concussion Update newsletter; please consider subscribing.

Veterans exposed to blast-induced mild traumatic brain injury (blast mTBI) may experience impaired function of the glymphatic system, according to a recent study published in Brain. (Blast mTBIs are “caused by exposure to a pressure wave from an explosion.”) In the first two parts of this three-part study, the brain tissue of veterans exposed to blast mTBI and the brains of mice who were exposed to similar blasts had abnormal expressions of aquaporin-4 (AQP4), a key part of the glymphatic system, which is responsible for clearing waste from the brain. In the clinical MRI section of the study, veterans exposed to blast mTBI showed signs of glymphatic dysfunction.

Molly Braun et al. concluded that exposure to blast TBI—which nearly half of the injured service members in the Iraq conflict experienced—may cause changes in AQP4, leading to dysfunction in the glymphatic system. The build-up of waste products in the brain is one factor in the development of neurodegenerative diseases such as Alzheimer’s and chronic traumatic encephalopathy (CTE). The authors also posit that glymphatic dysfunction may underly common comorbidities such as depression and post-traumatic stress disorder.

Additionally, higher glymphatic dysfunction in living veterans “may contribute to the development and persistence” of post-concussion symptoms. The study found that glymphatic dysfunction was “associated with the persistence of a wide range of post-concussive symptoms,” with these symptoms lasting, on average, 4-5 years after an individual’s last blast mTBI. They also found that poor sleep appears to worsen glymphatic function in those exposed to blast mTBI, so therapeutic sleep interventions may improve glymphatic function and symptom outcomes for these patients.

Braun et al.’s study consisted of three main components. The first part of the study examined how much and where APQ4 appeared in the brain tissue of deceased veterans who had experienced blast TBI. Compared to the brains of veterans with no exposure to blast TBI, veterans with blast TBI history had abnormal expression of AQP4. To test whether these changes in AQP4 were associated with glymphatic system dysfunction, the researchers exposed mice to repetitive blast mTBI to mimic what veterans had experienced. In blast-exposed mice, AQP4 changes similar to those of humans were observed. The mice with abnormal AQP4 expression also had impaired glymphatic function. Finally, the study used neuroimaging to examine the perivascular spaces in the veterans’ donated brain tissue. Perivascular spaces are fluid-filled spaces around blood vessels that are part of the glymphatic system. The authors found a higher number of enlarged perivascular spaces, indicating glymphatic dysfunction, in veterans exposed to blast TBI.

Braun et al.’s findings illustrate the impacts of blast TBI on the glymphatic system, which can have long-lasting effects on brain and psychological health in veterans. Prior research has linked impaired functioning of the glymphatic system to increases in amyloid beta and tau proteins, both of which are associated with CTE and Alzheimer’s Disease. Still, further research is required to fully understand the relationship that AQP4 and the glymphatic system have on outcomes after blast mTBI––with respect to both persisting symptoms and long-run neurodegenerative disease.

Call for study participants: military veterans who have had concussions and/or a traumatic brain injury, including any injury to your head or neck that caused you to lose consciousness or feel dazed/confused/experience a gap in memory. This includes brain injury resulting from exposure to blasts. Your participation in research could help inform the future of TBI treatment for fellow veterans.