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Publication : Impaired meningeal lymphatic vessel development worsens stroke outcome.

First Author  Yanev P Year  2020
Journal  J Cereb Blood Flow Metab Volume  40
Issue  2 Pages  263-275
PubMed ID  30621519 Mgi Jnum  J:339485
Mgi Id  MGI:7522588 Doi  10.1177/0271678X18822921
Citation  Yanev P, et al. (2020) Impaired meningeal lymphatic vessel development worsens stroke outcome. J Cereb Blood Flow Metab 40(2):263-275
abstractText  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.
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