Subarachnoid hemorrhage (SAH) is characterized by the extravasation of blood into the subarachnoid space, in which erythrocyte lysis is the primary contributor to cell death and brain injuries. New evidence has indicated that meningeal lymphatic vessels (mLVs) are essential in guiding fluid and macromolecular waste from cerebrospinal fluid (CSF) into deep cervical lymph nodes (dCLNs). However, the role of mLVs in clearing erythrocytes after SAH has not been completely elucidated. Hence, we conducted a cross-species study. Autologous blood was injected into the subarachnoid space of rabbits and rats to induce SAH. Erythrocytes in the CSF were measured with/without deep cervical lymph vessels (dCLVs) ligation. Additionally, prior to inducing SAH, we administered rats with vascular endothelial growth factor C (VEGF-C), which is essential for meningeal lymphangiogenesis and maintaining integrity and survival of lymphatic vessels. The results showed that the blood clearance rate was significantly lower after dCLVs ligation in both the rat and rabbit models. DCLVs ligation aggravated neuroinflammation, neuronal damage, brain edema, and behavioral impairment after SAH. Conversely, the treatment of VEGF-C enhanced meningeal lymphatic drainage of erythrocytes and improved outcomes in SAH. In summary, our research highlights the indispensable role of the meningeal lymphatic pathway in the clearance of blood and mediating consequences after SAH.

中文翻译：

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颈部淋巴管结扎会减慢血液清除速度，导致实验性蛛网膜下腔出血后的结果恶化

蛛网膜下腔出血（SAH）的特点是血液外渗到蛛网膜下腔，其中红细胞溶解是细胞死亡和脑损伤的主要原因。新证据表明，脑膜淋巴管（mLV）对于引导脑脊液（CSF）中的液体和大分子废物进入颈深淋巴结（dCLN）至关重要。然而，mLV 在 SAH 后清除红细胞中的作用尚未完全阐明。因此，我们进行了一项跨物种研究。将自体血液注射到兔和大鼠的蛛网膜下腔中以诱导SAH。在有/没有颈深淋巴管 (dCLV) 结扎的情况下测量 CSF 中的红细胞。此外，在诱导 SAH 之前，我们给大鼠注射血管内皮生长因子 C (VEGF-C)，这对于脑膜淋巴管生成和维持淋巴管的完整性和存活至关重要。结果显示，大鼠和兔模型中dCLVs结扎后的血液清除率均显着降低。DCLV结扎加重了SAH后的神经炎症、神经元损伤、脑水肿和行为障碍。相反，VEGF-C 治疗可增强红细胞的脑膜淋巴引流并改善 SAH 的预后。总之，我们的研究强调了脑膜淋巴通路在血液清除和介导 SAH 后后果中不可或缺的作用。