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Updated: Sep 24, 2025
Isolating Central Nervous System Tissues and Associated Meninges for the Downstream Analysis of Immune cells
Published on: May 19, 2020
Meningeal lymphatic vessels mediate neurotropic viral drainage from the central nervous system
Xiaojing Li1,2,3,4, Linlin Qi1,2,4, Dan Yang2,4
1Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, China.
Abstract:
Recent studies have demonstrated that brain meningeal lymphatic vessels (MLVs) act as a drainage path directly into the cervical lymph nodes (CLNs) for macromolecules contained in the cerebrospinal fluid (CSF). However, the role of MLVs during CNS viral infection remains unexplored. Here, we found that infection with several neurotropic viruses in mice promotes MLV expansion but also causes impaired MLV-mediated drainage of macromolecules. Notably, MLVs could drain virus from the CNS to CLNs. Surgical ligation of the lymph vessels or photodynamic ablation of dorsal MLVs increased neurological damage and mortality of virus-infected mice. By contrast, pretreatment with vascular endothelial growth factor C promoted expansion of functional MLVs and alleviated the effects of viral infection. Together, these data indicate that functional MLVs facilitate virus clearance, and MLVs represent a critical path for virus spreading from the CNS to the CLNs. MLV-based therapeutic strategies may thus be useful for alleviating infection-induced neurological damage.
Insights
Brain lymphatic vessels (MLVs) drain cerebrospinal fluid (CSF) but their role in viral infections is unknown. This study shows MLVs clear viruses from the CNS, but infection impairs drainage, highlighting MLVs as a therapeutic target.
Area of Science:
- Neuroimmunology
- Vascular Biology
- Infectious Diseases
Background:
- Brain meningeal lymphatic vessels (MLVs) drain cerebrospinal fluid (CSF) macromolecules to cervical lymph nodes (CLNs).
- The function of MLVs during central nervous system (CNS) viral infections is not well understood.
Purpose of the Study:
- To investigate the role of MLVs in CNS viral infections.
- To determine if MLVs are involved in virus clearance or spread from the CNS.
Main Methods:
- Mice were infected with neurotropic viruses.
- MLV function was assessed through macromolecule drainage assays.
- MLV drainage was manipulated via surgical ligation and photodynamic ablation.
- Vascular endothelial growth factor C (VEGF-C) was used to promote MLV expansion.
Main Results:
- Viral infection caused MLV expansion but impaired drainage.
- MLVs were found to drain virus from the CNS to CLNs.
- Disruption of MLVs worsened neurological damage and mortality.
- VEGF-C treatment enhanced MLV function and reduced disease severity.
Conclusions:
- Functional MLVs are crucial for clearing viruses from the CNS.
- MLVs serve as a pathway for virus dissemination from the CNS to CLNs.
- Targeting MLVs may offer a therapeutic strategy for CNS viral infections.
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