Traumatic Brain Injury Blog

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Damage to the Brain’s Lymphatic System May Explain Why Some Patients Suffer More Serious Consequences from TBI

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Studies over the last several years have shown that the lymphatic system serving the brain, located in the membranes covering the brain (the “meninges”) plays an important role in brain injury recovery.

As most people know, the lymphatic system helps to rid the body of toxins and waste, including the byproducts of the body’s immune response to injury. For brain injury this is sometimes described as “damage/danger-associated molecular patterns” – “DAMPs” – such as protein aggregates, necrotic cells, and cellular debris.

Researchers at the University of Virginia, at the Center for Brain Immunology and Glia, have released an important study furthering our understanding of the role meningeal lymphatic dysfunction plays in causing some patients to suffer severe and long-lasting impairments following even a “mild” traumatic brain injury (TBI) and helps to explain why these injuries increase the risk for neurodegenerative problems such as Alzheimer’s, ALS and dementia. Ashley C. Bolte, Arun B. Dutta, Mariah E. Hurt, Igor Smirnov, Michael A. Kovacs, Celia A. McKee, Hannah E. Ennerfelt, Daniel Shapiro, Bao H. Nguyen, Elizabeth L. Frost, Catherine R. Lammert, Jonathan Kipnis, John R. Lukens. Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis. Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-18113-4

The research also provides insight into why a prior brain injury, especially one that has not fully recovered, and even the aging process, can worsen prognosis following a brain injury.

Tissue damage and cellular stress resulting from TBI activates the immune system, which is intended to aide in the disposal of neurotoxic material and coordinate tissue repair. Unfortunately, unchecked and/or chronic immune activation can lead to secondary tissue damage, brain atrophy and neurological dysfunction. The UVA team offers evidence that compromises in meningeal lymphatic drainage, caused by a prior brain injury (or by age or genetic predisposition) can lead to a destructive accumulation of neurotoxic DAMPs in the brain and lead to more severe consequences.

One important finding is that “a single mild head injury can result in pronounced disruptions in meningeal lymphatic function.” This finding underscores the importance of policies preventing athletes from returning to competition until fully recovered from concussion symptoms and further explains why patients with a history of TBI are more vulnerable to lasting symptoms.

On a positive note, the study finds that meningeal lymphatic function may be boosted through delivery of an endothelial growth factor such as VEGF-C. Although this study involved mice, it holds out the promise of new therapeutic approaches for human TBI.

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