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Effect of VEGF-C treatment on sorted brain microglia/macrophages

ABSTRACT: Effect of VEGF-C treatment on sorted brain microglia/macrophages

PROVIDER: PRJNA1061529 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27441380_1.fastq.gz	Fastqsanger.gz
	SRR27441380_2.fastq.gz	Fastqsanger.gz
	SRR27441381_1.fastq.gz	Fastqsanger.gz
	SRR27441381_2.fastq.gz	Fastqsanger.gz
	SRR27441382_1.fastq.gz	Fastqsanger.gz

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Effect of VEGF-C treatment on sorted brain microglia/macrophages

Project description: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. Intra-cerebrospinal 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 ligation 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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