A comparison of neuroinflammation to implanted microelectrodes in rat and mouse models

Abstract

Rat models have emerged as a common tool to study neuroinflammation to intracortical microelectrodes. While a number of studies have attempted to understand the factors resulting in neuroinflammation using rat models, a complete understanding of key mechanistic pathways remains elusive. Transgenic mouse models, however, could facilitate a deeper understanding of mechanistic pathways due to an ease of genetic alteration. Therefore, the goal of the present study is to compare neuroinflammation following microelectrode implantation between the rat and the mouse model. Our study suggests that subtle differences in the classic neuroinflammatory markers exist between the animal models at both two and sixteen weeks post implantation. Most notably, neuronal densities surrounding microelectrodes were significantly lower in the rat model at two weeks, while similar densities were observed between the animal models at sixteen weeks. Physiological differences between the species and slight alterations in surgical methods are likely key contributors to the observed differences. Moving forward, we propose that differences in the time course of neuroinflammation between the animal models should be considered when trying to understand and prevent intracortical microelectrode failure.

Mechanically-compliant intracortical implants reduce the neuroinflammatory response

“…Surgical procedures for device implantation closely followed an established protocol, with only minor changes (8, 20, 21). Briefly, twenty-six male Sprague Dawley rats (250 – 300 grams) (Charles River, Spencerville, OH) received implants and were euthanized after three days or two, eight, or sixteen weeks.…”

The roles of blood-derived macrophages and resident microglia in the neuroinflammatory response to implanted Intracortical microelectrodes

“…To assess propagation of neuroinflammatory events following microelectrode implantation, a sterile, single-shank, non-functional ‘Michigan-style’ silicon microelectrode (2 mm × 123 μm × 15 μm) was implanted in wildtype and chimera mice for two, four, eight or sixteen weeks according to previously published protocols [29,30]. All surgeries in this study were performed in a class II sterile hood by the same surgeon to minimize infection and variability, respectively.…”

“…At two, four, eight and sixteen weeks post implantation, mice were perfused and brain tissue was cryoprotected according to methods previously described [29,30]. Briefly, mice were anesthetized with an intraperitoneal (IP) injection of rodent cocktail (150 μl 100 mg/ml Ketamine HCl, 150 μl 20 mg/ml Xylazine HCl, 50 μl 10 mg/ml Acepromazine).…”

“…Immunohistological (IHC) analysis of neuroinflammatory associated cellular markers (microglia/macrophages, activated microglia/macrophages and astrocytes) as well as blood protein Immunoglobulin G (IgG) was performed in wildtype and chimera mice to quantify the extent of the neuroinflammatory response at the tissue–electrode interface, as previously described [29,30]. Additionally, IHC analysis of CFP+ cells was also performed in chimera mice in order to quantify the populations of infiltrating blood-derived cells over time surrounding the microelectrode.…”

“…Neuronal densities were assessed using diaminobenzidine (DAB) histochemistry following the methods previously described [29,30]. Tissue sections were equilibrated to RT and permeated as described in Section 2.7.1.…”