Impaired Meningeal Lymphatic Vessel Development Worsens Stroke Outcome

Authors

Pavel Yanev, University of Texas Southwestern Medical Center
Katherine Poinsatte, University of Texas Southwestern Medical Center
Devon Hominick, University of Texas Southwestern Medical Center
Noor Khurana, University of Texas Southwestern Medical Center
Kielen R. Zuurbier, University of Texas Southwestern Medical Center
Marcus Berndt, University of Texas Southwestern Medical Center
Erik J. Plautz, University of Texas Southwestern Medical Center
Michael T. Dellinger, University of Texas Southwestern Medical Center
Ann M. Stowe, University of KentuckyFollow

Abstract

The discovery of meningeal lymphatic vessels (LVs) has sparked interest in identifying their role in diseases of the central nervous system. Similar to peripheral LVs, meningeal LVs depend on vascular endothelial growth factor receptor-3 (VEGFR3) signaling for development. Here we characterize the effect of stroke on meningeal LVs, and the impact of meningeal lymphatic hypoplasia on post-stroke outcomes. We show that photothrombosis (PT), but not transient middle cerebral artery occlusion (tMCAo), induces meningeal lymphangiogenesis in young male C57Bl/J6 mice. We also show that Vegfr3^wt/mut mice develop significantly fewer meningeal LVs than Vegfr3^wt/wt mice. Again, meningeal lymphangiogenesis occurs in the alymphatic zone lateral to the sagittal sinus only after PT-induced stroke in Vegfr3^wt/wt mice. Interestingly, Vegfr3^wt/mut mice develop larger stroke volumes than Vegfr3^wt/wt mice after tMCAo, but not after PT. Our results reveal differences between PT and tMCAo models of stroke and underscore the need to consider method of stroke induction when investigating the role of meningeal lymphatics. Taken together, our data indicate that ischemic injury can induce the growth of meningeal LVs and that the absence of these LVs can impact post-stroke outcomes.

Document Type

Article

Publication Date

2-1-2020

Notes/Citation Information

Published in Journal of Cerebral Blood Flow and Metabolism, v. 40, issue 2.

© Author(s) 2019

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

Digital Object Identifier (DOI)

https://doi.org/10.1177/0271678X18822921

Funding Information

This study was funded by grants to A.M.S. from the American Heart Association (14SDG18410020), NIH/NINDS (NS088555), the Dana Foundation (David Mahoney Neuroimaging grant), and The Haggerty Center for Brain Injury and Repair (UTSW). The WBMF is supported by the Texas Institute for Brain Injury and Repair (TIBIR).

Repository Citation

Yanev, Pavel; Poinsatte, Katherine; Hominick, Devon; Khurana, Noor; Zuurbier, Kielen R.; Berndt, Marcus; Plautz, Erik J.; Dellinger, Michael T.; and Stowe, Ann M., "Impaired Meningeal Lymphatic Vessel Development Worsens Stroke Outcome" (2020). Neurology Faculty Publications. 52.
https://uknowledge.uky.edu/neurology_facpub/52