Antioxidant Dimethyl Fumarate Temporarily but Not Chronically Improves Intracortical Microelectrode Performance

Abstract

Intracortical microelectrode arrays (MEAs) can be used in a range of applications, from basic neuroscience research to providing an intimate interface with the brain as part of a brain-computer interface (BCI) system aimed at restoring function for people living with neurological disorders or injuries. Unfortunately, MEAs tend to fail prematurely, leading to a loss in functionality for many applications. An important contributing factor in MEA failure is oxidative stress resulting from chronically inflammatory-activated microglia and macrophages releasing reactive oxygen species (ROS) around the implant site. Antioxidants offer a means for mitigating oxidative stress and improving tissue health and MEA performance. Here, we investigate using the clinically available antioxidant dimethyl fumarate (DMF) to reduce the neuroinflammatory response and improve MEA performance in a rat MEA model. Daily treatment of DMF for 16 weeks resulted in a significant improvement in the recording capabilities of MEA devices during the sub-chronic (Weeks 5–11) phase (42% active electrode yield vs. 35% for control). However, these sub-chronic improvements were lost in the chronic implantation phase, as a more exacerbated neuroinflammatory response occurs in DMF-treated animals by 16 weeks post-implantation. Yet, neuroinflammation was indiscriminate between treatment and control groups during the sub-chronic phase. Although worse for chronic use, a temporary improvement (<12 weeks) in MEA performance is meaningful. Providing short-term improvement to MEA devices using DMF can allow for improved use for limited-duration studies. Further efforts should be taken to explore the mechanism behind a worsened neuroinflammatory response at the 16-week time point for DMF-treated animals and assess its usefulness for specific applications.

Reactive Amine Functionalized Microelectrode Arrays Provide Short-Term Benefit but Long-Term Detriment to In Vivo Recording Performance

“…Homogenized samples were sent to the Gene Expression and Genotyping Facility at Case Western Reserve University for RNA isolation. ,, The RNeasy Plus Universal Mini Kit (Qiagen 73404) was used to isolate the RNA. Nanodrop and TapeStation systems were used to check the RNA quantity.…”

“…Substantial efforts to develop new MEA architectures include devices with ultrathin shank dimensions or low modulus of elasticity materials to create flexible devices which aim to mitigate the tissue-device mechanical mismatch. − In addition, administration of pharmacological compounds postimplantation have been investigated including the use of dexamethasone, , resveratrol, dimethyl fumarate, and minocycline . Several groups have recently explored the use of bioactive coatings, with the goal to mitigate neuroinflammation related to decreased chronic recording performance.…”

Effects of micromachining on anti-oxidant elution from a mechanically-adaptive polymer

“…Neural recording sessions were done to evaluate recording performance from the MARE probes, following established protocols [63][64][65]. Animals were anesthesized with 2.5% isoflurane gas, and the exposed connector was then cleaned with isopropanol.…”

In Vivo Characterization of Intracortical Probes with Focused Ion Beam-Etched Nanopatterned Topographies

“…Two auxiliary craniotomies were created using a 1.35 mm drill bit (Stoelting Co., USA) for the insertion of the ground and reference screws (stainless steel bone screws, Stoelting Co., Wood Dale, IL, USA), hand-drilled into the skull turning only 2.5 times to prevent touching brain tissue, both positioned 1.5 mm to the left lateral of the midline and 1.5 mm (ground) and 5.5 mm (reference) posterior to the bregma. A final craniotomy was created using a 1.35 mm drill bit for an anchoring screw (1.5 mm lateral and 3 mm posterior to bregma) to help secure the dental cement to the skull following established protocols [50].…”

“…RNA samples were hybridized with a reporter codeset and capture codeset. The reporter codeset contains fluorescent probes for a custom panel of 152 genes of interest (Table 1) [27,[50][51][52][53][54], including six housekeeping genes (HK). The panel was selected based on significant genes from our previous studies and available oxidative stress markers [41,51,55,56].…”