Implantation of Neural Probes in the Brain Elicits Oxidative Stress

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.

Neuroinflammation, oxidative stress, and blood-brain barrier (BBB) disruption in acute Utah electrode array implants and the effect of deferoxamine as an iron chelator on acute foreign body response

“…However, electrode insertion induces a rampant foreign body response that activates NADPH oxidase (NOX) (Figure 7B) in multiple cell types acting as phagocytes, especially microglia, to produce reactive oxygen and nitrogen species [108–115], which can be referred to as a respiratory burst [116]. In fact, Potter et al [117] and Ereifej et al [118] demonstrated the presence of superoxide anions and the oxidation of nucleic acids, lipids, and proteins, respectively, surrounding electrode sites, confirming local oxidative stress at electrode sites.…”

Investigating the Association between Motor Function, Neuroinflammation, and Recording Metrics in the Performance of Intracortical Microelectrode Implanted in Motor Cortex

“…Surgical procedures were similar to our previously published methods [ 12 , 20 , 40 , 41 ]. Six male Sprague Dawley rats (8–10 weeks old, ~225 gm) were implanted with silicon, single shank, 16 channel intracortical microelectrodes (NeuroNexus A1x16-3mm-100-177-Z16, NeuroNexus, Ann Arbor, MI, USA) in the primary motor cortex (2mm lateral to midline and 2mm anterior to bregma) for eight weeks.…”

“…The implantation of the IME severs vasculature, thus breaching the blood–brain barrier and initiating the inflammatory response [ 14 , 15 , 16 ]. Local microglia and infiltrating macrophages become activated, releasing cytokines, neurotoxic factors, and reactive oxygen species (ROS) [ 17 , 18 , 19 , 20 , 21 ]. The release of cytokines, neurotoxic factors, and ROS around implanted electrodes results in a perpetual foreign body response, death of neurons, and corrosion and delamination of the microelectrode surface [ 20 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

The Future of Neuroimplantable Devices: A Materials Science and Regulatory Perspective

“…As covered in Section 2, many of the functional properties and risk factors associated with neuroimplantable devices stem from material selections and form factor. [120] However, the surgical protocols and methods for implantation, i.e., the implantation procedure, have been shown to greatly contribute to clinical safety concerns, [121,122] fidelity of interfacing, [123] and efficacy of treatment. [123] Historically, the implantation of neural probes-including epicortical systems like ECoG, intracortical systems like the Utah array, and deep brain systems like DBS-have required the use of stereotactic craniotomy.…”