Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis

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

Research output: Contribution to journalReview articlepeer-review

25 Scopus citations

Abstract

Traumatic brain injury (TBI) is a leading global cause of death and disability. Here we demonstrate in an experimental mouse model of TBI that mild forms of brain trauma cause severe deficits in meningeal lymphatic drainage that begin within hours and last out to at least one month post-injury. To investigate a mechanism underlying impaired lymphatic function in TBI, we examined how increased intracranial pressure (ICP) influences the meningeal lymphatics. We demonstrate that increased ICP can contribute to meningeal lymphatic dysfunction. Moreover, we show that pre-existing lymphatic dysfunction before TBI leads to increased neuroinflammation and negative cognitive outcomes. Finally, we report that rejuvenation of meningeal lymphatic drainage function in aged mice can ameliorate TBI-induced gliosis. These findings provide insights into both the causes and consequences of meningeal lymphatic dysfunction in TBI and suggest that therapeutics targeting the meningeal lymphatic system may offer strategies to treat TBI.

Original languageEnglish
Article number4524
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

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