Through the NOSE! Non-invasive Modulation of CSF Absorption

In a proof of concept paper, Harold Kim, PhD, and colleagues tested if intranasal drug delivery (delivery through a nasal spray) could increase cerebrospinal fluid (CSF) absorption through the lymphatic system. The lymphatic system helps maintain fluid balance by draining excess fluid into the bloodstream. Certain drugs can increase this fluid drainage through the lymphatic vessels by either increasing phasic contractility or, conversely, inhibiting vessel contractions. In other words, flow through the vessels can be increased by either increasing their ability to pump the fluid out, or by completely relaxing the vessel so that fluid can flow more freely.

In an HA-funded study, Dr. Kim with Sara Moore and Miles Johnston, PhD, hypothesized that intranasal delivery of these drugs would influence lymphatic vessels at the cribriform plate. The cribriform plate is located at the juncture of the nose and forehead. It is perforated, allowing direct connections between CSF and the lymphatic system. The cribriform plate is therefore an area where drugs given in the form of a nasal mist are able to directly affect CSF extra-cranial drainage.

Published this past year in Fluids and Barriers of the CNS, their paper, Potential for intranasal drug delivery to alter cerebrospinal fluid outflow via the nasal turbinate lymphatics, showed that two drugs already known to modulate lymphatic vessel contractility could increase CSF outflow rates at high intracranial pressures.

Although in its early stages, this promising research provides evidence that a drug could increase the amount of fluid that is being drained by the lymphatic system and thereby provide relief from building intracranial pressure due to CSF accumulation. Further, a simple delivery method, such as a nasal spray, much like you might use to unblock a stuffy nose when you have a cold, could provide a non-surgical means to manage hydrocephalus. While this is just a proof of concept today, with further research and development, this brings us closer to finding alternative or supplemental treatment methods for hydrocephalus.

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Dr. Kim is part of the Angiogenic Signaling Group at the Sunnybrook Research Institute in Toronto, CAN. Dr. Johnston was part of the Lymphatic Research Group at Sunnybrook and was one of two 2011 Hydrocephalus Association CSF Award grantees. He is now a Professor Emeritus in the Department of Laboratory Medicine and Pathobiology at the University of Toronto.