murine-model-cerebral-venous-outflow-occlusion-through-bilateral

Murine Model of Cerebral Venous Outflow Occlusion Through Bilateral Ligation of Jugular Veins

Lymphatic vessels play a key role in maintaining fluid homeostasis and immune surveillance within tissues. At the brain's border, the dural meninges ...

Sorbonne Université

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.

VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model.

Correlation between natural history and multi-omics profiling of meningiomas in NF2-related schwannomatosis suggests role of methylation group and immune microenvironment in tumor growth rate.

Article	Year
VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model. The Journal of experimental medicine\| PubMed ID: 38442272	2024
Correlation between natural history and multi-omics profiling of meningiomas in NF2-related schwannomatosis suggests role of methylation group and immune microenvironment in tumor growth rat... Acta neuropathologica\| PubMed ID: 39192083	2024

Ruchith Singhabahu

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