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NOVEL METHODS OF THERMALLY MEDIATED SELECTIVE NEURAL INHIBITION

Zhuo, Junqi
http://orcid.org/0000-0003-4260-768X
http://rave.ohiolink.edu/etdc/view?acc_num=case1679575656810625

Abstract Details

2023, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Small-diameter axons (e.g., unmyelinated C fibers) are commonly afferent axons that carry critical sensory signals. Selective inhibition of dysfunctional small-diameter axons can be useful for basic neuroscience research and lead to treatments for neurological diseases (e.g., neuropathic pain and persistent hypertension), but remains an unmet need. Conventional pharmaceutical targets are distributed throughout the body, which causes systematic side effects. Electrode-based neuromodulation modalities tend to block large-diameter axons first. Other efforts, such as multi-electrode designs, have achieved spatial selectivity, which is challenged by the degradation of electrode performance due to immune responses. There is a need for a modality that can intrinsically and reliably induce size-selective inhibition of small-diameter axons. Our lab and collaborators have demonstrated in previous studies that infrared (IR) neural inhibition (INI) can selectively inhibit small-diameter axons via the heat induced by the absorption of IR light (e.g., 1470 nm, 1860 nm) which thermally accelerates ion9 channel dynamics. In this work, we first explored the possibility of lowering the IR power threshold for INI with isotonic ion replacement using glucose and/or choline in the extracellular fluid. We applied IR and isotonic ion replacement simultaneously to the same nerve segment, both at a sub-threshold level, and the results confirmed that the IR power threshold of size-selective INI can be lowered by isotonic ion replacement. Second, we tested the hypothesis that resistive heating can reproduce the size selectivity of INI. We fabricated a customized resistive heating cuff and tested localized heat application via both resistive heating and INI on the same nerve. The experimental results confirmed that resistive heating can reproduce the size-selective inhibition on small-diameter axons with higher overall energy efficiency. Further numerical simulation showed that INI and resistive heating required similar temperature elevations on the axons for the same inhibitory effect. In addition to the two projects, related preliminary methods and test results are included in the appendix. Here, we present efforts to provide modalities for size-selective inhibition on small-diameter axons. Further studies in this direction can help researchers and physicians explore the functionalities of small-diameter axons and develop future therapeutic options.
Andrew Rollins (Committee Chair)
Michael Jenkins (Committee Member)
Kenneth Laurita (Committee Member)
Dustin Tyler (Committee Member)
Hillel Chiel (Committee Member)
180 p.
Biomedical Engineering
Neuromodulation, infrared neural inhibition, infrared neural stimulation, selective inhibition, small-diameter axons, resistive heating

Recommended Citations

Citations

  • Zhuo, J. (2023). NOVEL METHODS OF THERMALLY MEDIATED SELECTIVE NEURAL INHIBITION [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1679575656810625

    APA Style (7th edition)

  • Zhuo, Junqi. NOVEL METHODS OF THERMALLY MEDIATED SELECTIVE NEURAL INHIBITION. 2023. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1679575656810625.

    MLA Style (8th edition)

  • Zhuo, Junqi. "NOVEL METHODS OF THERMALLY MEDIATED SELECTIVE NEURAL INHIBITION." Doctoral dissertation, Case Western Reserve University, 2023. http://rave.ohiolink.edu/etdc/view?acc_num=case1679575656810625

    Chicago Manual of Style (17th edition)

case1679575656810625
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© 2023, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.