Dual role of vascular endothelial growth factor-C in post-stroke recovery.

IF 12.6 1区医学 Q1 IMMUNOLOGY

Journal of Experimental Medicine Pub Date : 2025-02-03 Epub Date: 2024-12-12 DOI:10.1084/jem.20231816

Yun Hwa Choi, Martin Hsu, Collin Laaker, Jenna Port, Kristóf G Kovács, Melinda Herbath, Heeyoon Yang, Peter Cismaru, Alexis M Johnson, Bailey Spellman, Kelsey Wigand, Matyas Sandor, Zsuzsanna Fabry

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引用次数: 0

Abstract

Cerebrospinal fluid (CSF), antigens, and antigen-presenting cells drain from the central nervous system (CNS) into lymphatic vessels near the cribriform plate and dura, yet the role of these vessels during stroke is unclear. Using a mouse model of ischemic stroke, transient middle cerebral artery occlusion (tMCAO), we demonstrate stroke-induced lymphangiogenesis near the cribriform plate, peaking at day 7 and regressing by day 14. Lymphangiogenesis is restricted to the cribriform plate and deep cervical lymph nodes and is regulated by VEGF-C/VEGFR-3 signaling. The use of a VEGFR-3 inhibitor prevented lymphangiogenesis and led to improved stroke outcomes at earlier time points, with no effects at later time points. VEGF-C delivery after tMCAO did not further increase post-stroke lymphangiogenesis, but instead induced larger brain infarcts. Our data support the damaging role of VEGF-C acutely and a pro-angiogenic role chronically. This nuanced understanding of VEGFR-3 and VEGF-C in stroke pathology advises caution regarding therapeutic VEGF-C use in stroke.

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血管内皮生长因子- c在脑卒中后恢复中的双重作用。

脑脊液（CSF）、抗原和抗原呈递细胞从中枢神经系统（CNS）流入筛状板和硬脑膜附近的淋巴管，但这些血管在中风中的作用尚不清楚。使用小鼠缺血性卒中，短暂性大脑中动脉闭塞（tMCAO）模型，我们在筛状板附近发现中风诱导的淋巴管生成，在第7天达到峰值，并在第14天消退。淋巴管生成局限于筛状板和颈深淋巴结，并受VEGF-C/VEGFR-3信号的调控。VEGFR-3抑制剂的使用阻止了淋巴管生成，并在早期时间点改善了卒中预后，在后期时间点没有效果。tMCAO后VEGF-C的输送并没有进一步增加脑卒中后淋巴管生成，而是引起更大的脑梗死。我们的数据支持VEGF-C的急性损伤作用和慢性促血管生成作用。对中风病理中VEGFR-3和VEGF-C的细微理解提示在中风治疗中使用VEGF-C要谨慎。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Experimental Medicine 医学-免疫学

CiteScore

26.60

自引率

1.30%

发文量

189

审稿时长

3-8 weeks

期刊介绍： Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field. Our unique editorial system, driven by a commitment to exceptional author service, involves two collaborative groups of editors: professional editors with robust scientific backgrounds and full-time practicing scientists. Each paper undergoes evaluation by at least one editor from both groups before external review. Weekly editorial meetings facilitate comprehensive discussions on papers, incorporating external referee comments, and ensure swift decisions without unnecessary demands for extensive revisions. Encompassing human studies and diverse in vivo experimental models of human disease, our focus within medical biology spans genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We eagerly welcome reports ranging from atomic-level analyses to clinical interventions that unveil new mechanistic insights.