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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Bolte AC,Dutta AB,Hurt ME,Smirnov I,Kovacs MA,McKee CA,Ennerfelt HE,Shapiro D,Nguyen BH,Frost EL,Lammert CR,Kipnis J,Lukens JRdoi
10.1038/s41467-020-18113-4subject
Has Abstractpub_date
2020-09-10 00:00:00pages
4524issue
1issn
2041-1723pii
10.1038/s41467-020-18113-4journal_volume
11pub_type
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