Reduced blood supply to the brain activates the intracranial inflammatory response, a key contributor to secondary brain damage in ischemic stroke. Post-stroke, activation of peripheral immune cells leads to systemic inflammatory responses. Usingin vivo approaches, we investigated meningeal lymphatics’ role in central immune cell infiltration and peripheral immune cell activation. The bilateral deep cervical lymph nodes (dCLNs) were removed 7 days before right middle cerebral artery occlusion in Sprague Dawley (SD) rats. At 3, 24, and 72 h post-intervention, brain immune cell infiltration and microglial and astrocyte activation were measured, while immune cells were classified in the spleen and blood. Inflammatory factor levels in peripheral blood were analyzed. Simultaneously, reverse verification was conducted by injecting AAV-vascular endothelial growth factor C (AAV-VEGFC) adenovirus into the lateral ventricle 14 days before middle cerebral artery occlusion (MCAO) induction to enhance meningeal lymph function. Blocking meningeal LVs in MCAO rats significantly reduced infarct area and infiltration, and inhibited microglia and pro-inflammatory astrocytes activation. After removing dCLNs, CD4 T lymphocytes, CD8 T lymphocytes, B lymphocytes, macrophages, and neutrophils in the spleen and blood of MCAO rats decreased significantly at different time points. The levels of inflammatory factors IL-6, IL-10, IL-1β, and TNF-α in plasma decreased significantly. Tests confirmed the results, and AAV-VEGFC-induced MCAO rats provided reverse validation.

中文翻译：

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阻断脑淋巴系统可减少缺血性中风的中枢和外周炎症反应

大脑供血减少会激活颅内炎症反应，这是缺血性中风继发性脑损伤的关键因素。中风后，外周免疫细胞的激活导致全身炎症反应。使用体内方法，我们研究了脑膜淋巴管在中枢免疫细胞浸润和外周免疫细胞激活中的作用。在 Sprague Dawley (SD) 大鼠右侧大脑中动脉闭塞前 7 天，切除双侧颈深淋巴结 (dCLN)。干预后3、24和72小时，测量脑部免疫细胞浸润以及小胶质细胞和星形胶质细胞活化，同时对脾脏和血液中的免疫细胞进行分类。分析外周血中炎症因子水平。同时，通过在大脑中动脉闭塞（MCAO）诱导前14天向侧脑室注射A​​AV-血管内皮生长因子C（AAV-VEGFC）腺病毒来增强脑膜淋巴功能进行反向验证。阻断 MCAO 大鼠的脑膜 LV 可显着减少梗塞面积和浸润，并抑制小胶质细胞和促炎星形胶质细胞的激活。去除dCLNs后，MCAO大鼠脾脏和血液中CD4 T淋巴细胞、CD8 T淋巴细胞、B淋巴细胞、巨噬细胞和中性粒细胞在不同时间点均明显减少。血浆中炎症因子IL-6、IL-10、IL-1β、TNF-α水平显着降低。测试证实了结果，AAV-VEGFC 诱导的 MCAO 大鼠提供了反向验证。