Subdural haematomas drain into the extracranial lymphatic system through the meningeal lymphatic vessels

Xuanhui Liu,Weiwei Jiang,Jiangyuan Yuan,Dong Wang,Hongliang Luo,Xintong Ge,Ping Lei,Zhitao Gong,Rongcai Jiang,Ye Tian,Yiming Song,Jianning Zhang,Jinhao Huang,Tangtang Xiang,Wei Quan,Chuang Gao

doi:10.1186/s40478-020-0888-y

Abstract

Subdural haematomas (SDHs) are characterized by rapidly or gradually accumulated haematomas between the arachnoid and dura mater. The mechanism of haematoma clearance has not been clearly elucidated until now. The meningeal lymphatic vessel (mLV) drainage pathway is a novel system that takes part in the clearance of waste products in the central nervous system (CNS). This study aimed to explore the roles of the mLV drainage pathway in SDH clearance and its impacting factors. We injected FITC-500D, A488-fibrinogen and autologous blood into the subdural space of mice/rats and found that these substances drained into deep cervical lymph nodes (dCLNs). FITC-500D was also observed in the lymphatic vessels (LYVE+) of the meninges and the dCLNs in mice. The SDH clearance rate in SDH rats that received deep cervical lymph vessel (dCLV) ligation surgery was significantly lower than that in the control group, as evaluated by haemoglobin quantification and MRI scanning. The drainage rate of mLVs was significantly slower after the SDH model was established, and the expression of lymphangiogenesis-related proteins, including LYVE1, FOXC2 and VEGF-C, in meninges was downregulated. In summary, our findings proved that SDH was absorbed through the mLV drainage pathway and that haematomas could inhibit the function of mLVs.

Highlights

The lymphatic system plays an important role in modulating tissue homeostasis, excess fluid clearance and macromolecule and immune cell migration [3, 6, 38]
We demonstrated the drainage role of meningeal lymphatic vessel (mLV) in Subdural hematoma (SDH) by detecting whether substances (FITC-500D, autologous blood, A488- fibrinogen) injected into the subdural space could drain into Deep cervical lymph node (dCLN) and by evaluating whether deep cervical lymph vessel (dCLV) ligation surgery can slow the processes of SDH clearance
Macromolecular fluorescein in the subdural space drained into dCLNs through the mLVs To test how the macromolecular waste in the subdural space was cleared, A488-fibrinogen, Evans Blue (EB) and FITC-500D were injected into the subdural space

Summary

Introduction

The lymphatic system plays an important role in modulating tissue homeostasis, excess fluid clearance and macromolecule and immune cell migration [3, 6, 38]. The central nervous system (CNS) was considered an organic system devoid of lymphatic vasculature until 2015, when two groups of researchers discovered lymphatic endothelial cells (LECs), which express classic lymphoid markers (LYVE 1, PROX 1, VEGF R3, FOXC 2 and podoplanin), and functional lymphatic vessels in the dura of rodents [1, 5, 24, 33]. It has been demonstrated that meningeal lymphatic vessels (mLVs) drain. Subdural haematomas (SDHs), the most common disease of the subdural space, progressively accumulate between the arachnoid and dura mater; SDHs consist of acute SDH, subacute SDH and chronic SDH (CSDH) [21, 32, 34]. CSDH is predicted to be one of the most common neurosurgical diseases, especially in individuals over 70 years old [21, 27, 28].

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