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    Layered Stimulus Patterning to Synergistically Optimize Brain Clearance at Multiple Points in Clearance System and Real-Time Dial to Change Drug Delivery Profiles
    1.
    发明公开
    Layered Stimulus Patterning to Synergistically Optimize Brain Clearance at Multiple Points in Clearance System and Real-Time Dial to Change Drug Delivery Profiles 审中-公开

    公开(公告)号：US20230381508A1

    公开(公告)日：2023-11-30

    申请号：US18201881

    申请日：2023-05-25

    申请人： Wisconsin Alumni Research Foundation

    发明人： Kip Ludwig ,  Justin Williams ,  Kevin Cheng ,  Nishant Verma

    IPC分类号： A61N1/36 ,  A61N1/04

    CPC分类号： A61N1/36025 ,  A61N1/0456 ,  A61N1/36034

    摘要： 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.