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Impaired meningeal lymphatic vessel development worsens stroke outcome.

Authors
  • Yanev, Pavel1
  • Poinsatte, Katherine1
  • Hominick, Devon2
  • Khurana, Noor2
  • Zuurbier, Kielen R1
  • Berndt, Marcus1
  • Plautz, Erik J1
  • Dellinger, Michael T2, 3
  • Stowe, Ann M1, 4
  • 1 Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 2 Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 3 Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 4 Department of Neurology, University of Kentucky, Lexington, KY, USA.
Type
Published Article
Journal
Journal of Cerebral Blood Flow & Metabolism
Publisher
SAGE Publications
Publication Date
Feb 01, 2020
Volume
40
Issue
2
Pages
263–275
Identifiers
DOI: 10.1177/0271678X18822921
PMID: 30621519
Source
Medline
Keywords
Language
English
License
Unknown

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 Vegfr3wt/mut mice develop significantly fewer meningeal LVs than Vegfr3wt/wt mice. Again, meningeal lymphangiogenesis occurs in the alymphatic zone lateral to the sagittal sinus only after PT-induced stroke in Vegfr3wt/wt mice. Interestingly, Vegfr3wt/mut mice develop larger stroke volumes than Vegfr3wt/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.

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