Significantly reduced inflammatory foreign-body-response to neuroimplants and improved recording performance in young compared to adult rats

Abstract

The multicellular inflammatory encapsulation of implanted intracortical multielectrode arrays (MEA) is associated with severe deterioration of their field potentials' (FP) recording performance, which thus limits the use of brain implants in basic research and clinical applications. Therefore, extensive efforts have been made to identify the conditions in which the inflammatory foreign body response (FBR) is alleviated, or to develop methods to mitigate the formation of the inflammatory barrier. Here, for the first time, we show that (1) in young rats (74±8 gr, 4 weeks old at the onset of the experiments), cortical tissue recovery following MEA implantation proceeds with ameliorated inflammatory scar as compared to adult rats (242±18 gr, 9 weeks old at the experimental onset); (2) in contrast to adult rats in which the Colony Stimulating factor 1 Receptor (CSF1R) antagonist chow eliminated ~95% of the cortical microglia but not microglia adhering to the implant surfaces, in young rats the microglia adhering to the implant were eliminated along with the parenchymal microglia population. The removal of microglia adhering to the implant surfaces was correlated with improved recording performance by in-house fabricated Perforated Polyimide MEA Platforms (PPMP). These results support the hypothesis that microglia adhering to the surface of the electrodes, rather than the multicellular inflammatory scar, is the major underlying mechanism that deteriorates implant recording performance, and that young rats provide an advantageous model to study months-long, multisite electrophysiology in freely behaving rats.

Advanced age is not a barrier to chronic intracortical single-unit recording in rat cortex

“…Lesion or stroke-like cavities have only been reported in rats in a subset of studies that used multi-shank microelectrode arrays in younger rats (Williams et al, 2007;Ward et al, 2009;Saxena et al, 2013;Black et al, 2018;Sharon et al, 2023), and not in those using simple planar single-shank silicon microelectrode arrays or with a few planar microelectrode shafts. Williams et al found significantly altered impedance spectra for microwires associated with lesions, but did record single units (Williams et al, 2007).…”

“…Similarly, older rats show increased loss of neural tissue following experimental injuries (Rosen et al, 2005;Kumar et al, 2013). A recent study using a single planar penetrating array in the rat cortex reported a significantly reduced FBR and improved recording performance over a six-week period in 4-week-old rats compared to a slightly older group (9 weeks at implantation) (Sharon et al, 2023). Moreover, clinical studies using deep brain stimulation (DBS) with devices implanted in older patients show increased rates of complications (Voges et al, 2007), decreased clinical benefit (Saint-Cyr et al, 2000;Charles et al, 2002;Welter et al, 2002), and increased rates of cognitive and behavioral impairment (Saint-Cyr et al, 2000).…”