Abstract
Clinical implantation of intracortical microelectrodes has been hindered, at least in part, by the perpetual inflammatory response occurring after device implantation. The neuroinflammatory response observed after device implantation has been correlated to oxidative stress that occurs due to neurological injury and disease. However, there has yet to be a definitive link of oxidative stress to intracortical microelectrode implantation. Thus, the objective of this study is to give direct evidence of oxidative stress following intracortical microelectrode implantation. This study also aims to identify potential molecular targets to attenuate oxidative stress observed postimplantation. Here, we implanted adult rats with silicon non-functional microelectrode probes for 4 weeks and compared the oxidative stress response to no surgery controls through postmortem gene expression analysis and qualitative histological observation of oxidative stress markers. Gene expression analysis results at 4 weeks postimplantation indicated that EH domain-containing 2, prion protein gene (Prnp), and Stearoyl-Coenzyme A desaturase 1 (Scd1) were all significantly higher for animals implanted with intracortical microelectrode probes compared to no surgery control animals. To the contrary, NADPH oxidase activator 1 (Noxa1) relative gene expression was significantly lower for implanted animals compared to no surgery control animals. Histological observation of oxidative stress showed an increased expression of oxidized proteins, lipids, and nucleic acids concentrated around the implant site. Collectively, our results reveal there is a presence of oxidative stress following intracortical microelectrode implantation compared to no surgery controls. Further investigation targeting these specific oxidative stress linked genes could be beneficial to understanding potential mechanisms and downstream therapeutics that can be utilized to reduce oxidative stress-mediated damage following microelectrode implantation.
Highlights
Intracortical microelectrodes were initially designed as a neuroscience tool to allow researchers the ability to investigate and understand how the nervous system works (Renshaw et al, 1940; Grundfest and Campbell, 1942; Grundfest et al, 1950)
Gene expression analysis was performed on both implanted and no surgery control animals in order to better understand the molecular markers involved in the oxidative stress pathway occurring after intracortical microelectrode implantation
Of the 84 genes analyzed in the array, there were four genes that revealed statistically significant differences between the surgery and sham animals (Table 2): EH domain-containing 2 (Ehd2), prion protein gene (Prnp), Stearoyl-Coenzyme A desaturase 1 (Scd1), and Nicotinamide adenine dinucleotide phosphate oxidase activator 1 (Noxa1)
Summary
Intracortical microelectrodes were initially designed as a neuroscience tool to allow researchers the ability to investigate and understand how the nervous system works (Renshaw et al, 1940; Grundfest and Campbell, 1942; Grundfest et al, 1950). In addition to their role as a research tool, intracortical microelectrodes have the ability to treat patients with a wide range of neurological injuries and.
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