Meningeal Lymphatic Vessels' Impact on Traumatic Brain Injury

"They'll have to rewrite the textbooks" - the discovery of meningeal lymphatic vessels

Meningeal lymphatic vessels were first discovered by Dr. Jonathan Kipnis and his colleagues from the University of Virginia in 2015. Around the brain and spinal cord, there is a clear, colorless body fluid called cerebrospinal fluid (CSF). Meningeal lymphatic vessels carry both fluid and immune cells from the CSF and are connected to the deep cervical lymph nodes. This discovery of the vessels explained the long-held concept of the absence of lymphatic vasculature in the CNS and led to a reassessment of basic assumptions in neuroimmunology.

 

In dissected mouse brains, the researchers found that meningeal lymphatic vessels possess anatomical and molecular features characteristic of initial lymphatic vessels but also some unique features that could be due to the high CSF pressure in the CNS. These unique features include covering less of the tissue, forming a less complex network composed of narrower vessels, and being larger and more complex in the transverse sinuses than in the superior sagittal sinus.

 

New Understandings About Traumatic Brain Injury

Five years later, researchers also from the University of Virginia have found that traumatic brain injury (TBI) is associated with damage of the meningeal lymphatic vessels and may lead to lasting impact, which was unknown in the past.

 

Meningeal Lymphatic Vessels and TBI

The researchers have found that even mild brain injuries may cause severe deficits in meningeal lymphatic drainage of the brain, which is the draining of immune cells, small molecules, and excess fluid from the CNS into the deep cervical lymph nodes. In a mild closed-skull model of TBI of mice, meningeal lymphatic drainage is altered and its capacity is likely to be affected by injury severity. When the brain swells inside the fixed skull, it puts pressure on the meningeal lymphatic vessels which are vulnerable due to the fact that they are not associated with smooth muscles.

 

Prior Lymphatic Injuries May Worsen TBI

The study also suggests that people who already have injuries of meningeal lymphatic vessels, either being born with a disease or due to concussion, are likely to endure more serious effects after traumatic brain injury. In the mice models, prior lymphatic defects worsen TBI-induced inflammation and memory losses. Furthermore, lymphatic rejuvenation mitigates TBI-driven inflammation.

 

References:

Bolte, Ashley C., et al. “Meningeal Lymphatic Dysfunction Exacerbates Traumatic Brain Injury Pathogenesis.” Nature Communications, vol. 11, no. 1, 2020.        Crossref, doi:10.1038/s41467-020-18113-4.

 

Louveau, Antoine, et al. “Structural and Functional Features of Central Nervous System Lymphatic Vessels.” Nature, vol. 523, no. 7560, 2015, pp. 337–41.                Crossref, doi:10.1038/nature14432.

Image: Writer, Gen Staff. “Lymphatic Vessels in Brain Provide New Route to Treat MS.” GEN - Genetic Engineering and Biotechnology News, 31 Oct. 2018, www.genengnews.com/news/lymphatic-vessels-in-brain-provide-new-route-to-treat-ms.

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