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Updated: Aug 1, 2025
Three-Dimensional Imaging of the Vertebral Lymphatic Vasculature and Drainage using iDISCO+ and Light Sheet Fluorescence Microscopy
Published on: May 22, 2020
Lymphatic vasculature in the central nervous system
Sara González-Hernández1, Yoh-Suke Mukouyama1
1Laboratory of Stem Cell and Neuro-Vascular Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.
Insights
The central nervous system (CNS) lacks lymphatic vessels in its parenchyma, unlike other organs. This study explores why these vessels don't develop within the brain's tissue, impacting immune responses.
Area of Science:
- Neuroscience
- Immunology
- Vascular Biology
Background:
- The central nervous system (CNS) is traditionally viewed as immune privileged, partly due to the absence of lymphatic vessels.
- The blood-brain barrier (BBB) and lack of CNS parenchymal lymphatics were thought to limit immune responses.
- Recent discoveries of lymphatic-like vessels in the meninges and eye challenge this view, but parenchymal lymphatics remain unconfirmed.
Purpose of the Study:
- To investigate the reasons behind the absence of lymphatic vessels within the CNS parenchyma.
- To explore potential mechanisms for lymphatic vasculature development in organs.
- To understand the implications for CNS immune privilege.
Main Methods:
- Review of existing literature on CNS immunity and lymphatic development.
- Analysis of proposed mechanisms for lymphatic vessel formation (sprouting vs. endothelial differentiation).
- Discussion of factors potentially inhibiting lymphatic development specifically within the CNS parenchyma.
Main Results:
- The CNS parenchyma lacks classical lymphatic vessels, contributing to its immune-privileged status.
- Lymphatic vessels can form via sprouting or endothelial cell differentiation.
- Specific factors within the CNS microenvironment may prevent lymphatic development.
Conclusions:
- The absence of lymphatic vessels in the CNS parenchyma is a key factor in its immune privilege.
- Understanding these inhibitory factors could reveal new therapeutic targets for CNS diseases.
- Further research is needed to confirm parenchymal lymphatic presence and function.
Abstract:
The central nervous system (CNS) is considered as an immune privilege organ, based on experiments in the mid 20th century showing that the brain fails to mount an efficient immune response against an allogeneic graft. This suggests that in addition to the presence of the blood-brain barrier (BBB), the apparent absence of classical lymphatic vasculature in the CNS parenchyma limits the capacity for an immune response. Although this view is partially overturned by the recent discovery of the lymphatic-like hybrid vessels in the Schlemm's canal in the eye and the lymphatic vasculature in the outmost layer of the meninges, the existence of lymphatic vessels in the CNS parenchyma has not been reported. Two potential mechanisms by which lymphatic vasculature may arise in the organs are: 1) sprouting and invasion of lymphatic vessels from the surrounding tissues into the parenchyma and 2) differentiation of blood endothelial cells into lymphatic endothelial cells in the parenchyma. Considering these mechanisms, we here discuss what causes the dearth of lymphatic vessels specifically in the CNS parenchyma.
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