VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model.
J Exp Med
; 221(4)2024 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-38442272
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acidente Vascular Cerebral
/
AVC Isquêmico
Limite:
Animals
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos