Nasal Lymphatic Network Crucial for Brain CSF Drainage

Summary: Researchers discovered a crucial network of lymphatic vessels at the back of the nose, which significantly contributes to draining cerebrospinal fluid (CSF) from the brain. This study reveals a previously unknown CSF outflow route, offering insights into neurodegenerative conditions.

The research team used transgenic mice with lymphatic markers and advanced imaging to uncover this network, which connects to deep cervical lymph nodes. Their findings indicate potential therapeutic targets for enhancing CSF drainage, especially in age-related neurodegenerative diseases.

Key Facts:

  1. The newly discovered nasopharyngeal lymphatic plexus is a major hub for CSF drainage from the brain.
  2. The study suggests that activating cervical lymphatics could improve CSF outflow, offering a new therapeutic approach for neurodegenerative diseases.
  3. The research team plans to validate these findings in primates, aiming to advance treatments for conditions like Alzheimer’s disease.

Source: Institute for Basic Science

In a groundbreaking study published in Nature, South Korean researchers led by Director KOH Gou Young of the Center for Vascular Research within the Institute for Basic Science (IBS) have uncovered a distinctive network of lymphatic vessels at the back of the nose that plays a critical role in draining cerebrospinal fluid (CSF) from the brain.

The study, sheds light on a previously unknown route for CSF outflow, potentially unlocking new avenues for understanding and treating neurodegenerative conditions.

In our brains, waste products generated as byproducts of metabolic activity are expelled through cerebrospinal fluid (CSF). Accumulation of waste in the brain, if not properly expelled, can damage nerve cells, leading to impaired cognitive function, dementia, and other neurodegenerative brain disorders.

This shows a head.
The brain produces around 500 mL of this fluid per day, which is drained from the subarachnoid space. Credit: Neuroscience News

Hence, the regulation of CSF production, circulation, and drainage has long been a focus of scientific attention, especially in relation to age-related conditions like Alzheimer’s disease and other neurodegenerative diseases.

The brain produces around 500 mL of this fluid per day, which is drained from the subarachnoid space. Among the known drainage routes are lymphatic vessels around the cranial nerves and the upper region of the nasal cavity.

Despite well-documented evidence of lymphatics aiding CSF clearance, identifying the exact anatomical connections between the subarachnoid space and extracranial lymphatics has posed a challenge due to their extremely complex structure.

Koh’s team tackled this problem using transgenic mice with lymphatic fluorescent markers, microsurgeries, and advanced imaging techniques. Their efforts revealed a detailed network of lymphatic vessels at the back of the nose that serves as a major hub for CSF outflow to deep cervical lymph nodes in the neck. These lymphatics were found to have distinct features, including unusually shaped valves and short lymphangions.

Lead researcher JIN Hokyung highlighted, “Our study identified the nasopharyngeal lymphatic plexus as a hub for CSF outflow. CSF from specific cranial regions drained through these lymphatics to deep cervical lymph nodes in the neck. This discovery could have significant implications for understanding and treating conditions related to impaired CSF drainage.”

The study also demonstrated that pharmacological activation of the deep cervical lymphatics enhanced CSF drainage in mice.

The researchers were able to successfully modulate cervical lymphatics using phenylephrine (which activates α1-adrenergic receptors, causing smooth-muscle contraction) or sodium nitroprusside (which releases nitric oxide, inducing muscle relaxation and vessel dilation).

Importantly, this feature was preserved during aging, even when the nasopharyngeal lymphatic plexus had shrunk and was functionally impaired.

YOON Jin-Hui, the co-first author of this study, notes, “The deep cervical lymphatics, which remain intact with aging, offer a potential target for therapeutic interventions aimed at improving CSF outflow in individuals with compromised brain health.”

This endeavor was not without its own challenges, however. Deep anesthesia and removal of neck musculature were required to expose the lymphatics in the mice.

These delicate procedures themselves had problems altering the physiological dynamics of CSF drainage because cerebral blood flow and blood pulsing through the vasculature contribute to CSF circulation, which in turn influences CSF outflow.

Also, while the imaging techniques used were informative, researchers believe more advanced methods for imaging live animals (such as synchrotron X-ray imaging) may reveal more features of the dynamics of CSF drainage under physiological conditions.

Director KOH Gou Young of the Center for Vascular Research stated, “We plan to verify all the findings from the mice in primates, including monkeys and humans. We aim to investigate in a reliable animal model whether activating the cervical lymphatic vessels through pharmacological or mechanical means can prevent the exacerbation of Alzheimer’s disease progression by improving CSF clearance.”

About this neuroscience research news

Author: William Suh
Source: Institute for Basic Science
Contact: William Suh – Institute for Basic Science
Image: The image is credited to Neuroscience News

Original Research: Open access.
Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage” by KOH Gou Young et al. Nature


Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage

Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes, but the connections and regulation have been challenging to identify.

Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes.

This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics.

During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines.

The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial.

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