Channels by which cerebrospinal fluid leaves the brain are important to long term health, as they allow removal of metabolic waste such as the protein aggregates that characterize neurodegenerative conditions. It is thought that atrophy of these channels, including (a) passage through the cribriform plate and (b) the comparatively recently discovered glymphatic system, contributes to the aging of the brain by allowing molecular waste to build up to levels that change cell behavior for the worse. Here researchers repeat in human patients the demonstrations of glymphatic drainage of cerebrospinal fluid that have been carried out in laboratory animals. Leucadia Therapeutics is developing an implant to restore passage through the cribriform plate, but it remains to be seen as to how the more complex dysfunction of the glymphatic system will be best addressed.
The glymphatic pathway was described as a network of perivascular spaces (PVS) that facilitates the organized movement of cerebrospinal fluid (CSF) between the subarachnoid space and brain parenchyma. CSF mixes with interstitial fluid, promoting clearance of soluble by-products from the central nervous system. This is suspected to be impaired in sleep dysfunction, traumatic brain injury, and Alzheimer's disease.
Pioneering glymphatic studies in rodents showed CSF tracer flow through the subarachnoid space and into brain parenchyma along periarterial spaces. Human intrathecal contrast-enhanced MRI similarly demonstrated parenchymal contrast enhancement in a centripetal pattern from the subarachnoid space, providing early evidence for human glymphatic function. The PVS is postulated to be involved in this process, yet perivascular CSF tracer transport has not been observed in humans. This is a proof-of-principle study in which, by using intrathecal gadolinium contrast-enhanced MRI, we show that contrast-enhanced CSF moves through the PVS into the parenchyma, supporting the existence of a glymphatic pathway in humans.
Link: https://doi.org/10.1073/pnas.2407246121
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