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. STATEMENT OF SIGNIFICANCE: Multisite electrophysiological recordings and stimulation devices play central roles in basic brain research and medical applications. The insertion of multielectrode-array platforms into the brain's parenchyma unavoidably injures the tissue, and initiates a multicellular inflammatory cascade culminating in the formation of an encapsulating scar tissue (the foreign body response-FBR). The dominant view, which directs most current research efforts to mitigate the FBR, holds that the FBR is the major hurdle to effective electrophysiological use of neuroprobes. By contrast, this report demonstrates that microglia adhering to the surface of a neuroimplants, rather than the multicellular FBR, underlie the performance deterioration of neuroimplants. These findings pave the way to the development of novel and focused strategies to overcome the functional deterioration of neuroimplants.