Several hypotheses have been proposed to explain how the brain tissue reaction to single unit recording electrodes influences biocompatibility including progressive changes in the spatial distribution of reactive astrocytes, and the loss of neurons over the indwelling period. To examine these hypotheses, the spatial distribution of biomarkers associated with the foreign body response to insulated microwires placed in rat cerebral cortex was analyzed 2, 4, and 12 weeks after implantation using quantitative methods. We observed a stereotypical tissue response that was similar in some aspects to that previously reported for penetrating planar silicon microelectrode arrays with some specific differences including an overall lower degree of cortical tissue reactivity. While we found no evidence that reactive gliosis increases over time or that neuronal loss is progressive, we did find evidence of persistent inflammation and enhanced BBB permeability at the electrode brain tissue interface that extended over the 3 month indwelling period and that exhibited more animal to animal variability at 3 months than at 2 and 4 weeks.
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