4.6 Article

Implications of chronic daily anti-oxidant administration on the inflammatory response to intracortical microelectrodes

Journal

JOURNAL OF NEURAL ENGINEERING
Volume 12, Issue 4, Pages -

Publisher

IOP PUBLISHING LTD
DOI: 10.1088/1741-2560/12/4/046002

Keywords

microelectrode; neural inflammation; oxidative stress

Funding

  1. Department of Biomedical Engineering and Case School of Engineering at Case Western Reserve University
  2. Department of Education Graduate Fellowship in neural engineering [GAANN:P200A100112]
  3. Medtronic Fellowship
  4. Department of Veterans Affairs Merit Review [B7122R]
  5. Presidential Early Career Award for Scientists and Engineers (PECASE)
  6. National Institute of Health (National Institute of Neurological Disorders and Stroke) [1R01NS082404-01A1]

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Objective. Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach. Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg(-1). The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/ neuroprotection following device implantation. Main results. Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance. Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.

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