View source for US Patent Application 18201881. Layered Stimulus Patterning to Synergistically Optimize Brain Clearance at Multiple Points in Clearance System and Real-Time Dial to Change Drug Delivery Profiles simplified abstract

=Layered Stimulus Patterning to Synergistically Optimize Brain Clearance at Multiple Points in Clearance System and Real-Time Dial to Change Drug Delivery Profiles=


==Organization Name==

[[:Category:Wisconsin Alumni Research Foundation|Wisconsin Alumni Research Foundation]]


[[Category:Wisconsin Alumni Research Foundation]]

==Inventor(s)==

[[:Category:Kip Ludwig of Middleton WI (US)|Kip Ludwig of Middleton WI (US)]][[Category:Kip Ludwig of Middleton WI (US)]]

[[:Category:Justin Williams of Cambridge WI (US)|Justin Williams of Cambridge WI (US)]][[Category:Justin Williams of Cambridge WI (US)]]

[[:Category:Kevin Cheng of Verona WI (US)|Kevin Cheng of Verona WI (US)]][[Category:Kevin Cheng of Verona WI (US)]]

[[:Category:Nishant Verma of Madison WI (US)|Nishant Verma of Madison WI (US)]][[Category:Nishant Verma of Madison WI (US)]]

==Layered Stimulus Patterning to Synergistically Optimize Brain Clearance at Multiple Points in Clearance System and Real-Time Dial to Change Drug Delivery Profiles - A simplified explanation of the abstract==


This abstract first appeared for US patent application 18201881 titled 'Layered Stimulus Patterning to Synergistically Optimize Brain Clearance at Multiple Points in Clearance System and Real-Time Dial to Change Drug Delivery Profiles

==Simplified Explanation==

- The patent application describes a method of using electrical stimulation to improve the clearance of waste biomolecules and drugs from the brain.
- Low frequency electrical stimulation is delivered to the cranial nerves during sleep to increase the presence and function of aquaporin-4 (AQP4) channels in the astrocytic endfeet surrounding blood vessels in the brain.
- Higher frequency stimulation is used in bursts to pulse the underlying artery and drive cerebrospinal fluid (CSF) penetration into the brain tissue, increasing movement and the probability of waste biomolecules interacting with sites for active transport out of the brain.
- During sleep, gamma frequency stimulation is used to promote a more phagocytic phenotype in glial cells, helping to break down waste biomolecules and misfolded proteins for clearance.
- The electrical stimulation can be adjusted to selectively modify CSF clearance, such as quickly clearing drug concentrations in the brain during an overdose.


==Original Abstract Submitted==

Administration of low frequency electrical stimulation of the cranial nerves delivered during sleep increases the presence and function of aquaporin-4 (AQP4) channels in the astrocytic endfeet surrounding descending arterioles in the brain. This underlying low frequency stimulation pattern is overlaid with temporally patterned ‘bursts’ of higher frequency stimulation to pulse the underlying artery to drive cerebrospinal fluid (CSF) penetration into the parenchyma. This also serves to create more movement in general within the parenchymal extracellular space to increase the probability of waste biomolecules to interact with sites for active transport out of the brain. During the period of sleep, these two layered patterns will be periodically replaced with multiple continuous periods of stimulation at gamma frequency to promote a more phagocytic phenotype in glial cells to help break down waste biomolecules and misfolded proteins for subsequent clearance. Administration of electrical stimulation can be selectively modified to adjust CSF clearance, for example, to quickly clear drug concentrations in the brain during an overdose.



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