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- All Subjects: Bioengineering
- Creators: Muthuswamy, Jitendran
Biomechanical Micromotion at the Neural Interface Modulates Intercellular Membrane Potential In-Vivo
Description
Brain micromotion is a phenomenon that arises from basic physiological functions such as respiration (breathing) and vascular pulsation (pumping blood or heart rate). These physiological processes cause small micro displacements of 2-4µm for vascular pulsation and 10-30µm for respiration, in rat models. One problem related to micromotion is the instability of the probe and its ability to acquire stable neural recordings in chronic studies. It has long been thought the membrane potential (MP) changes due to micromotion in the presence of brain implants were an artefact caused by the implant. Here is shown that intracellular membrane potential changes are a consequence of the activation of mechanosensitive ion channels at the neural interface. A combination of aplysia and rat animal models were used to show activation of mechanosensitive ion channels is occurring during a neural recording. During simulated micromotion of displacements of 50μm and 100μm at a frequency of 1 Hz, showed a change of 8 and 10mV respectively and that the addition of Ethylenediaminetetraacetic acid (EDTA) inhibited the membrane potential changes. The application of EDTA showed a 71% decrease in changes in membrane potential changes due to micromotion. Simulation of breathing using periodic motion of a probe in an Aplysia model showed that there were no membrane potential changes for <1.5kPa and action potentials were observed at >3.1kPa. Drug studies utilizing 5-HT showed an 80% reduction in membrane potentials. To validate the electrophysiological changes due to micromotion in a rat model, a double barrel pipette for simultaneous recording and drug delivery was designed, the drug delivery tip was recessed from the recording tip no greater than 50μm on average. The double barrel pipette using iontophoresis was used to deliver 30 μM of Gadolinium Chloride (Gd3+) into the microenvironment of the cell. Here is shown a significant reduction in membrane potential for n = 13 cells across 4 different rats tested using Gd3+. Membrane potential changes related to breathing and vascular pulsation were reduced between approximately 0.25-2.5 mV for both breathing and heart rate after the addition of Gd3+, a known mechanosensitive ion channel blocker.
ContributorsDuncan, Jonathan Leroy (Author) / Muthuswamy, Jitendran (Thesis advisor) / Greger, Bradley (Committee member) / Sridharan, Arati (Committee member) / Arizona State University (Publisher)
Created2020
Description
Magnetic resonance imaging (MRI) is a noninvasive imaging modality, which is used for many different applications. The versatility of MRI is in acquiring high resolution anatomical and functional images with no use of ionizing radiation. The contrast in MR images can be engineered by two different mechanisms with imaging parameters (TR, TE, α) and/or contrast agents. The contrast in the former is influenced by the intrinsic properties of the tissue (T1, T2, ρ), while the contrast agents change the relaxation rate of the protons to enhance contrast. Contrast agents have attracted a lot of attention because they can be modified with targeting groups to shed light on some physiological and biological questions, such as the presence of hypoxia in a tissue. Hypoxia, defined as lack of oxygen, has many known ramifications on the outcome of therapy in any condition. Hence its study is very important. The standard gold method to detect hypoxia, immunohistochemical (IHC) staining of pimonidazole, is invasive; however, there are many research groups focused on developing new and mainly noninvasive methods to investigate hypoxia in different tissues.Previously, a novel nitroimidazole-based T1 contrast agent, gadolinium tetraazacyclododecanetetraacetic acid monoamide conjugate of 2-nitroimidazole (GdDO3NI ), has been synthesized and characterized on subcutaneous prostate and lung tumor models. Here, its efficacy and performance on traumatic brain injuries and brain tumors are studied. The pharmacokinetic properties of the contrast agent the perfusion properties of brain tumors are investigated. These results can be used in personalized therapies for more effective results for patients.
Gadolinium (Gd), which is a strongly paramagnetic heavy metal, is routinely and widely used as an MR contrast agent by chelation with a biocompatible ligand which is typically cleared through the kidneys. While widely used, there are serious concerns for patients with impaired kidney function, as well as recent studies showed Gd accumulation in the bone and brain. Iron as a physiological ion is also capable of generating contrast in MR images. Here synthesis and characterization of an iron-based hypoxia targeting contrast agent is proposed to eliminate Gd-related complications and provide a cheaper and more economical alternative contrast agent to detect hypoxia.
ContributorsMoghadas, Babak (Author) / Kodibagkar, Vikram D (Thesis advisor) / Beeman, Scott (Committee member) / Muthuswamy, Jitendran (Committee member) / Nikkhah, Mehdi (Committee member) / Turner, Gregory (Committee member) / Arizona State University (Publisher)
Created2021
Description
Electrical nerve stimulation is a promising drug-free technology that could treat a variety of ailments and disorders. Methods like Vagus Nerve Stimulation have been used for decades to treat disorders like epilepsy, and research with non-invasive vagus nerve stimulation has shown similar effects as its invasive counterpart. Non-invasive nerve stimulation methods like vagus nerve stimulation could help millions of people treat and manage various disorders.
This study observed the effects of three different non-invasive nerve stimulation paradigms in human participants. The first study analyzed the safety and efficacy of transcutaneous auricular vagal nerve stimulation in healthy humans using a bilateral stimulation protocol with uniquely designed dry-hydrogel electrodes. Results demonstrate bilateral auricular vagal nerve stimulation has significant effects on specific parameters of autonomic activity and is safe and well tolerated. The second study analyzed the effects of non-invasive electrical stimulation of a region on the side of the neck that contains the Great Auricular Nerve and the Auricular Branch of the Vagus Nerve called the tympanomastoid fissure on golf hitting performance in healthy golfers. Results did not show significant effects on hitting performance or physiological activity, but the nerve stimulation had significant effects on reducing state-anxiety and improving the quality of feel of each shot. The third study analyzed the effects of non-invasive nerve stimulation of cervical nerves on the back of the neck on putting performance of yips-affected golfers. Results demonstrated that cervical nerve stimulation had significant effects on improving putting performance but did not have significant effects on physiological activity. Data from these studies show there are potential applications for non-invasive electrical nerve stimulation for healthy and athletic populations. Future research should also examine the effects of these stimulation methods in clinical populations.
This study observed the effects of three different non-invasive nerve stimulation paradigms in human participants. The first study analyzed the safety and efficacy of transcutaneous auricular vagal nerve stimulation in healthy humans using a bilateral stimulation protocol with uniquely designed dry-hydrogel electrodes. Results demonstrate bilateral auricular vagal nerve stimulation has significant effects on specific parameters of autonomic activity and is safe and well tolerated. The second study analyzed the effects of non-invasive electrical stimulation of a region on the side of the neck that contains the Great Auricular Nerve and the Auricular Branch of the Vagus Nerve called the tympanomastoid fissure on golf hitting performance in healthy golfers. Results did not show significant effects on hitting performance or physiological activity, but the nerve stimulation had significant effects on reducing state-anxiety and improving the quality of feel of each shot. The third study analyzed the effects of non-invasive nerve stimulation of cervical nerves on the back of the neck on putting performance of yips-affected golfers. Results demonstrated that cervical nerve stimulation had significant effects on improving putting performance but did not have significant effects on physiological activity. Data from these studies show there are potential applications for non-invasive electrical nerve stimulation for healthy and athletic populations. Future research should also examine the effects of these stimulation methods in clinical populations.
ContributorsHool, Nicholas (Author) / Tyler, William J (Thesis advisor) / Crews, Debbie (Committee member) / Muthuswamy, Jitendran (Committee member) / Helms Tillery, Stephen (Committee member) / Sebold, Brent (Committee member) / Arizona State University (Publisher)
Created2020