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 and John R. Lukens ()
Additional contact information
Ashley C. Bolte: University of Virginia
Arun B. Dutta: University of Virginia
Mariah E. Hurt: University of Virginia
Igor Smirnov: University of Virginia
Michael A. Kovacs: University of Virginia
Celia A. McKee: University of Virginia
Hannah E. Ennerfelt: University of Virginia
Daniel Shapiro: University of Virginia
Bao H. Nguyen: University of Virginia
Elizabeth L. Frost: University of Virginia
Catherine R. Lammert: University of Virginia
Jonathan Kipnis: University of Virginia
John R. Lukens: University of Virginia

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-18113-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18113-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-18113-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().