Fight Aging!

Considerable progress has been made in recent years in mapping the pathways by which cerebrospinal fluid drains from the brain into the body, many of which were only recently discovered. The present consensus is that the progressive loss of this drainage with advancing age is likely important in the development of neurodegenerative conditions, allowing molecular waste such as amyloid-β to build up in the brain. Researchers here discuss a new branch of the system of cerebrospinal fluid drainage that passes behind the nose. Like the related cribriform plate pathway, this makes it off interest in the development of Alzheimer's disease, as the pathology of this condition starts in a nearby region of the brain.

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. 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.

Researchers 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. 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.

Link: https://www.ibs.re.kr/cop/bbs/BBSMSTR_000000000738/selectBoardArticle.do?nttId=24483