Meningeal lymphatics clear erythrocytes that arise from subarachnoid hemorrhage

Nat Commun. 2020 Jun 22;11(1):3159. doi: 10.1038/s41467-020-16851-z.

Abstract

Extravasated erythrocytes in cerebrospinal fluid (CSF) critically contribute to the pathogenesis of subarachnoid hemorrhage (SAH). Meningeal lymphatics have been reported to drain macromolecules and immune cells from CSF into cervical lymph nodes (CLNs). However, whether meningeal lymphatics are involved in clearing extravasated erythrocytes in CSF after SAH remains unclear. Here we show that a markedly higher number of erythrocytes are accumulated in the lymphatics of CLNs and meningeal lymphatics after SAH. When the meningeal lymphatics are depleted in a mouse model of SAH, the degree of erythrocyte aggregation in CLNs is significantly lower, while the associated neuroinflammation and the neurologic deficits are dramatically exacerbated. In addition, during SAH lymph flow is increased but without significant lymphangiogenesis and lymphangiectasia. Taken together, this work demonstrates that the meningeal lymphatics drain extravasated erythrocytes from CSF into CLNs after SAH, while suggesting that modulating this draining may offer therapeutic approaches to alleviate SAH severity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries
  • Erythrocytes
  • Lymph Nodes / physiopathology
  • Lymphangiogenesis
  • Lymphatic System / pathology*
  • Lymphatic Vessels / physiopathology
  • Male
  • Meninges / pathology*
  • Meningitis / etiology
  • Meningitis / pathology
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Neck
  • Subarachnoid Hemorrhage / cerebrospinal fluid
  • Subarachnoid Hemorrhage / pathology*
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism

Substances

  • Vascular Endothelial Growth Factor Receptor-3