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Functional And Histological Assessment Of Novel Microelectrode Arrays For Intraneural Recording Of Autonomic Neural Activity
Amir Dehdashtian, MD, Daniel C. Ursu, PhD, Paras R. Patel, PhD, Ahmad A. Jiman, Elissa Welle, Dongxiao Yan, PhD, David C. Ratze, Elizabeth C. Bottorff, Hannah J. Parrish, Zhonghua Ouyang, Euisik Yoon, PhD, Paul S. Cederna, MD, Tim R. Bruns, PhD, Cynthia A. Chestek, PhD, John P. Seymour, PhD, Stephen WP Kemp, PhD.
University of Michigan, Ann Arbor, MI, USA.

PURPOSE: As the field of bio-electronic medicine grows, so does the demand for advanced electrical interfaces that can provide highly selective stimulation and recording to improve clinical therapies. In particular, vagus nerve stimulation has shown benefits in treating tinnitus, diabetes, and rheumatoid arthritis. Unfortunately, current neural cuff and intrafascicular electrodes lack the spatial resolution necessary for extracting detailed neural activity. We have developed, and are assessing two microneedle arrays for interfacing with small autonomic nerves such as the vagus.
METHODS: Using a custom 3D-printed nerve hook, we implanted microneedle nerve arrays (MINA) of twenty-four 140 μm long electrodes into the left cervical vagus nerve of rodents (Fig.1A). Micro-CT of the electrode needles and harvested nerve were assessed post-implantation, along with osmium stained histomorphometry and immunohistochemical analysis of neural tissue cross-sections. We also implanted functional carbon fiber microelectrode arrays (CFMA) consisting of up to sixteen electrodes (each with a length of 200 μm) in rodent cervical vagus and peroneal nerves for acute recordings, followed by histomorphometric and histologic analysis.
RESULTS:A majority of MINA arrays remained intact in the vagus nerve at 1 week (Fig. 1B) and at 6 weeks post-implantation. Histomorphometric (Fig. 1C) and histologic analysis (Fig. 1D) of MINA-implanted nerves demonstrated thickly myelinated fibers and mature vasculature with minimal fibrosis despite nerve deformation. Neural recordings were obtained with CFMA in the vagus nerve in response to glucose infusions and in the peroneal nerve in response to cutaneous brushing. Histomorphometric analysis of acutely implanted CFMA vagus nerve fibers (Fig.2B & 2D) revealed myelinated fiber parameters similar to controls (Fig.2A & 2C). Development of functional MINA and chronic CFMA are on-going.
CONCLUSION:Both microelectrode arrays show potential for high-fidelity interfacing in the vagus nerve and other autonomic nerves across acute and chronic timeframes. These advanced neural interfaces may lead to more efficient neural stimulation therapies targeting a broad array of autonomic nerve disorders.


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