VEGF-C promotes brain-derived fluid drainage, confers neuroprotection, and improves stroke outcomes
VEGF-C promotes brain-derived fluid drainage, confers neuroprotection, and improves stroke outcomes
Abstract Meningeal lymphatic vessels promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelium growth factor-C (VEGF-C) is essential for meningeal lymphatic development and maintenance and has therapeutic potential for treating neurological disorders, including ischemic stroke. We have investigated the effects of VEGF-C overexpression on brain fluid drainage, single cell transcriptome in the brain, and stroke outcomes in adult mice. Intra-cerebrospinal fluid administration of an adeno-associated virus expressing VEGF-C (AAV-VEGF-C) increases the CNS lymphatic network. Post-contrast T1 mapping of the head and neck showed that deep cervical lymph node size and drainage of CNS-derived fluids were increased. Single nuclei RNA sequencing revealed a neuro-supportive role of VEGF-C via upregulation of calcium and brain-derived neurotrophic factor (BDNF) signaling pathways in brain cells. In a mouse model of ischemic stroke, AAV-VEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage. AAV-VEGF-C thus promotes CNS-derived fluid and solute drainage, confers neuroprotection, and reduces ischemic stroke damage. Short abstractIntrathecal delivery of VEGF-C increases the lymphatic drainage of brain-derived fluids confers neuroprotection, and improves neurological outcomes after ischemic stroke.
Parent Maxime、Zhang Shenqi、Osherov Artem、Alitalo Kari、Sansing Lauren H.、Spajer Myriam、Sestan Nenad、Skarica Mario、Askanase Michael、Eichmann Anne、Kamouh Marie-Renee El、Thomas Jean-Leon、Lee Seyoung、Xue Yuechuan、Bouchart Jean、Li Mingfeng、Sanganahalli Basavaraju G.、Simoes Braga Boisserand Ligia、Guegan Justine、Liu Xiodan、Poulet Mathilde、Benveniste Helene、Geraldo Luiz Henrique、Zhou Jiangbing、Hyder Fahmeed
Department of Radiology & Biomedical Imaging, Yale UniversityDepartment of Biomedical Engineering, Yale University||Department of Neurosurgery, Yale University School of MedicineDepartment of Immunobiology, Yale School of MedicineWihuri Research Institute and Translational Cancer Biology Program, Faculty of Medicine, University of HelsinkiDepartment of Neurology, Yale University School of Medicine||Department of Immunobiology, Yale School of MedicineParis Brain InstituteDepartment of Neuroscience, Yale School of Medicine||Kavli Institute for Neuroscience, Yale School of Medicine||Department of Genetics, Yale School of Medicine||Department of Psychiatry, Yale School of Medicine||Department of Comparative Medicine||Yale Child Study Center, Yale School of Medicine||Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale School of MedicineDepartment of Neurology, Yale University School of Medicine||Department of Neuroscience, Yale School of Medicine||Kavli Institute for Neuroscience, Yale School of MedicineDepartment of Immunobiology, Yale School of MedicineCardiovascular Research Center, Yale University School of Medicine||Department of Cellular and Molecular Physiology, Yale School of Medicine||INSERM U970, Paris Cardiovascular Research CenterParis Brain InstituteDepartment of Neurology, Yale University School of Medicine||Paris Brain InstituteDepartment of Neurology, Yale University School of MedicineDepartment of Anesthesiology, Yale School of MedicineDepartment of Neurology, Yale University School of MedicineDepartment of Neuroscience, Yale School of Medicine||Kavli Institute for Neuroscience, Yale School of MedicineDepartment of Radiology & Biomedical Imaging, Yale UniversityDepartment of Neurology, Yale University School of MedicineParis Brain InstituteDepartment of Anesthesiology, Yale School of MedicineCardiovascular Research Center, Yale University School of Medicine||Paris Brain InstituteDepartment of Anesthesiology, Yale School of MedicineCardiovascular Research Center, Yale University School of MedicineDepartment of Biomedical Engineering, Yale UniversityDepartment of Radiology & Biomedical Imaging, Yale University||Department of Biomedical Engineering, Yale University
神经病学、精神病学基础医学生物科学研究方法、生物科学研究技术
CSFmeningeal lymphaticsVEGF-Cneuroprotectionischemic stroke
Parent Maxime,Zhang Shenqi,Osherov Artem,Alitalo Kari,Sansing Lauren H.,Spajer Myriam,Sestan Nenad,Skarica Mario,Askanase Michael,Eichmann Anne,Kamouh Marie-Renee El,Thomas Jean-Leon,Lee Seyoung,Xue Yuechuan,Bouchart Jean,Li Mingfeng,Sanganahalli Basavaraju G.,Simoes Braga Boisserand Ligia,Guegan Justine,Liu Xiodan,Poulet Mathilde,Benveniste Helene,Geraldo Luiz Henrique,Zhou Jiangbing,Hyder Fahmeed.VEGF-C promotes brain-derived fluid drainage, confers neuroprotection, and improves stroke outcomes[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/2023.05.30.542708.点此复制
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