Medical Bionics - Research Publications

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    Abdominal vagus nerve stimulation alleviates collagen-induced arthritis in rats
    Payne, SC ; Romas, E ; Hyakumura, T ; Muntz, F ; Fallon, JB (FRONTIERS MEDIA SA, 2022-11-21)
    Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease. Despite therapeutic advances, a significant proportion of RA patients are resistant to pharmacological treatment. Stimulation of the cervical vagus nerve is a promising alternative bioelectric neuromodulation therapeutic approach. However, recent clinical trials show cervical vagus nerve stimulation (VNS) was not effective in a significant proportion of drug resistant RA patients. Here we aim to assess if abdominal vagus nerve stimulation reduces disease severity in a collagen-induced arthritis (CIA) rat model. The abdominal vagus nerve of female Dark Agouti rats was implanted and CIA induced using collagen type II injection. VNS (1.6 mA, 200 μs pulse width, 50 μs interphase gap, 27 Hz frequency) was applied to awake freely moving rats for 3 h/day (days 11-17). At 17 days following the collagen injection, unstimulated CIA rats (n = 8) had significantly worse disease activity index, tumor necrosis factor-alpha (TNF-α) and receptor activator of NFκB ligand (RANKL) levels, synovitis and cartilage damage than normal rats (n = 8, Kruskal-Wallis: P < 0.05). However, stimulated CIA rats (n = 5-6) had significantly decreased inflammatory scores and ankle swelling (Kruskal-Wallis: P < 0.05) compared to unstimulated CIA rats (n = 8). Levels of tumor necrosis factor-alpha (TNF-α) remained at undetectable levels in stimulated CIA rats while levels of receptor activator of NFκB ligand (RANKL) were significantly less in stimulated CIA rats compared to unstimulated CIA rats (P < 0.05). Histopathological score of inflammation and cartilage loss in stimulated CIA rats were no different from that of normal (P > 0.05). In conclusion, abdominal VNS alleviates CIA and could be a promising therapy for patients with RA.
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    Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model
    Payne, SC ; Ward, G ; Fallon, JB ; Hyakumura, T ; Prins, JB ; Andrikopoulos, S ; MacIsaac, RJ ; Villalobos, J (WILEY, 2022-04)
    Vagus nerve stimulation is emerging as a promising treatment for type 2 diabetes. Here, we evaluated the ability of stimulation of the vagus nerve to reduce glycemia in awake, freely moving metabolically compromised rats. A model of type 2 diabetes (n = 10) was induced using a high-fat diet and low doses of streptozotocin. Stimulation of the abdominal vagus nerve was achieved by pairing 15 Hz pulses on a distal pair of electrodes with high-frequency blocking stimulation (26 kHz, 4 mA) on a proximal pair of electrodes to preferentially produce efferent conducting activity (eVNS). Stimulation was well tolerated in awake, freely moving rats. During 1 h of eVNS, glycemia decreased in 90% of subjects (-1.25 ± 1.25 mM h, p = 0.017), and 2 dB above neural threshold was established as the most effective "dose" of eVNS (p = 0.009). Following 5 weeks of implantation, eVNS was still effective, resulting in significantly decreased glycemia (-1.7 ± 0.6 mM h, p = 0.003) during 1 h of eVNS. There were no overt changes in fascicle area or signs of histopathological damage observed in implanted vagal nerve tissue following chronic implantation and stimulation. Demonstration of the biocompatibility and safety of eVNS in awake, metabolically compromised animals is a critical first step to establishing this therapy for clinical use. With further development, eVNS could be a promising novel therapy for treating type 2 diabetes.
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    Improving Deep Brain Stimulation Electrode Performance in vivo Through Use of Conductive Hydrogel Coatings
    Hyakumura, T ; Aregueta-Robles, U ; Duan, W ; Villalobos, J ; Adams, WK ; Poole-Warren, L ; Fallon, JB (FRONTIERS MEDIA SA, 2021-11-05)
    Active implantable neurological devices like deep brain stimulators have been used over the past few decades to treat movement disorders such as those in people with Parkinson's disease and more recently, in psychiatric conditions like obsessive compulsive disorder. Electrode-tissue interfaces that support safe and effective targeting of specific brain regions are critical to success of these devices. Development of directional electrodes that activate smaller volumes of brain tissue requires electrodes to operate safely with higher charge densities. Coatings such as conductive hydrogels (CHs) provide lower impedances and higher charge injection limits (CILs) than standard platinum electrodes and support safer application of smaller electrode sizes. The aim of this study was to examine the chronic in vivo performance of a new low swelling CH coating that supports higher safe charge densities than traditional platinum electrodes. A range of hydrogel blends were engineered and their swelling and electrical performance compared. Electrochemical performance and stability of high and low swelling formulations were compared during insertion into a model brain in vitro and the formulation with lower swelling characteristics was chosen for the in vivo study. CH-coated or uncoated Pt electrode arrays were implanted into the brains of 14 rats, and their electrochemical performance was tested weekly for 8 weeks. Tissue response and neural survival was assessed histologically following electrode array removal. CH coating resulted in significantly lower voltage transient impedance, higher CIL, lower electrochemical impedance spectroscopy, and higher charge storage capacity compared to uncoated Pt electrodes in vivo, and this advantage was maintained over the 8-week implantation. There was no significant difference in evoked potential thresholds, signal-to-noise ratio, tissue response or neural survival between CH-coated and uncoated Pt groups. The significant electrochemical advantage and stability of CH coating in the brain supports the suitability of this coating technology for future development of smaller, higher fidelity electrode arrays with higher charge density requirement.