Impaired meningeal lymphatic vessel development worsens stroke outcome.
Open accessAbstract
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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Lymphangiogenesis was seen following photothrombotic stroke lesion in the mouse cortex, but this effect was not seen following MCAO.
“lymphangiogenesis was seen following photothrombotic stroke lesion in the mouse cortex, but this effect was not seen following MCAO”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Yanev et al., 2020
Blockage of VEGFR3 in mice following focal cerebral ischemia resulted in reduced inflammatory response and infarct, while VEGFR3 mutant mice subjected to MCAO develop larger stroke volumes and worsened edema.
“Blockage of VEGFR3 (expressed by lymphatic endothelial cells) in mice following focal cerebral ischemia resulted in reduced inflammatory response and infarct”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Yanev et al., 2020
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“However, VEGFR3 mutant mice subjected to MCAO develop larger stroke volumes, thus worsened edema (Yanev et al., 2020).”
Background
- Authors
- Yanev, P., Poinsatte, K., Hominick, D., Khurana, N., Zuurbier, K. R., Berndt, M., Plautz, E. J., Dellinger, M. T., & Stowe, A. M.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Kentucky (US)
- Corresponding author
- Dellinger, Michael T
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2019-01-09
- Volume
- 40
- Issue
- 2
- Pages
- 263-275
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC7370617
- OpenAlex
- W2909855888
- Cited by
- 126
- References
- 43
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 25 · 2023: 20 · 2022: 25 · 2021: 16 · 2020: 9 · 2019: 6
- FWCI
- 5.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- UKnowledge (University of Kentucky) (submittedVersion, cc-by-nc)
- Funders
- American Heart Association
- University of Texas Southwestern Medical Center
- Medical Research Council
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- meningeal lymphatic vessels, stroke, lymphangiogenesis, VEGFR-3, photothrombosis, transient middle cerebral artery occlusion, stroke outcome, ischemic injury, stroke model, superior sagittal sinus
- MeSH terms
- Glymphatic System, Animals, Disease Models, Animal, Male, Mice, Transgenic, Stroke, Vascular Endothelial Growth Factor Receptor-3, Lymphangiogenesis, Mice
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