Artikel ; Online: VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model.
The Journal of experimental medicine
2024 Band 221, Heft 4
Abstract: Meningeal lymphatic vessels (MLVs) promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelial growth factor-C (VEGF-C) regulates MLV development and maintenance and has therapeutic potential for treating ... ...
Abstract | Meningeal lymphatic vessels (MLVs) promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelial growth factor-C (VEGF-C) regulates MLV development and maintenance and has therapeutic potential for treating neurological disorders. Herein, we investigated the effects of VEGF-C overexpression on brain fluid drainage and ischemic stroke outcomes in mice. Intracerebrospinal administration of an adeno-associated virus expressing mouse full-length VEGF-C (AAV-mVEGF-C) increased CSF drainage to the deep cervical lymph nodes (dCLNs) by enhancing lymphatic growth and upregulated neuroprotective signaling pathways identified by single nuclei RNA sequencing of brain cells. In a mouse model of ischemic stroke, AAV-mVEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage, associated with mitigated microglia-mediated inflammation and increased BDNF signaling in brain cells. Neuroprotective effects of VEGF-C were lost upon cauterization of the dCLN afferent lymphatics and not mimicked by acute post-stroke VEGF-C injection. We conclude that VEGF-C prophylaxis promotes multiple vascular, immune, and neural responses that culminate in a protection against neurological damage in acute ischemic stroke. |
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Mesh-Begriff(e) | Animals ; Mice ; Vascular Endothelial Growth Factor C ; Neuroinflammatory Diseases ; Ischemic Stroke ; Drainage ; Stroke |
Chemische Substanzen | Vascular Endothelial Growth Factor C |
Sprache | Englisch |
Erscheinungsdatum | 2024-03-05 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article |
ZDB-ID | 218343-2 |
ISSN | 1540-9538 ; 0022-1007 |
ISSN (online) | 1540-9538 |
ISSN | 0022-1007 |
DOI | 10.1084/jem.20221983 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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