Objective. Neuroinflammation has long been associated with the performance decline of intracortical microelectrodes (IMEs). Consequently, several strategies, including the use of anti-inflammatories, have been employed to mitigate the inflammation surrounding IMEs. However, these strategies have had limited success towards achieving a chronically viable cortical neural interface, questioning the efficacy of anti-inflammatory approach. Approach. Herein, we conducted a systematic study in rats implanted with functional devices by modulating inflammation via systemic injection of lipopolysaccharide (LPS), dexamethasone (DEX), a combination of both, or none to assess the degree of inflammation on device functionality. We hypothesized that implanted rats treated with LPS will have a negative impact, and rats treated with DEX will have a positive impact on functionality IMEs and histological outcome. Main results. Contrary to our hypothesis, we did not observe adverse effects in recording metrics among different groups with LPS and/or DEX treatment despite alterations in initial pro-inflammatory markers. We also did not observe any functional benefit of anti-inflammatory treatment. Regardless of the treatment conditions, the recording quality degraded at chronic time points. In end-point histology, implanted rats that received LPS had significantly lower NeuN density and higher levels of CD68 surrounding the implant site, indicative of the pro-inflammatory effect of LPS, which, however, contradicted with the recorded results. Significance. Collectively, our results suggest that acute inflammatory events may not be the key driver for functional degradation of IMEs. Future intervention strategies geared towards improving the functional longevity of intracortical devices may benefit using multi-modal approaches rather than a single approach, such as controlling the initial inflammatory response.

To screen the complex central nervous system (CNS) injury responses, we created a quadruple-labelled ‘PrismPlus’ mouse line with a genetically encoded distinct fluorescent tag in oligodendrocytes, microglia, neurons, and astrocytes. Cx3cr1-gfp and Prism mice originally developed by Jung et al., 2000 and Dougherty et al., 2012, respectively, were cross-bred. First, we confirmed the presence of fluorophores in appropriate cell types in PrismPlus mice. PrismPlus mice were then used to examine the cellular responses to brain implanted micro-devices. We observed an increase in microglial response at earlier time points as compared to 4 weeks, a progressive astrocytic response, and fewer neurons at the vicinity of an implanted device. These results are similar to what has been described in literature using other rodent strains, previously attainable only through time-consuming and variable immunohistochemistry methods. Finally, we demonstrate the compatibility of PrismPlus brain tissue with CLARITY, an advanced tissue clearing technique, opening the door to future thick tissue imaging studies. This report confirms PrismPlus transgenic fluorescence and highlights the utility of these mice to study CNS injuries. The work herein seeks to establish a novel transgenic mouse line to improve experimental scope, consistency, and efficiency for CNS researchers.

No abstract