thesisPrevious studies indicate that the brain tissue reaction to implanted silicon recording microelectrode arrays involves hyperplasia of macrophages, microglia and astrocytes, and that these reactions are accompanied by a decrease in the density of neurons immediately surrounding the implant. It is generally believed that the foreign body response is a major factor in the inconsistent recording performance observed with these devices. To gain insight into the earliest events, we used immunohistochemical methods to characterize the cellular responses adjacent to implanted microelectrodes at 1 ,3 , and 7 days after implantation using single shank planar Michigan-style silicon microelectrode arrays implanted into the cortex of adult male Sprague Dawley rats (225-300g) with N=12 per time point. Electrodes were implanted using stereotactic positioning at +0.2 mm bregma, 3 mm lateral, and 2 mm deep and were anchored with photo-cured adhesive into a polyurethane grommet. As a control, stab wounds were created in the same method, with N=6 at 3 and 7 days. Animals were sacrificed by transcardial perfusion and serial sectioned with a vibrotome. Significant variability existed in the amount of surface hemorrhage and the presence of infracted blood vessels along the implantation tract. Activated macrophages were attached to explanted probes at all postimplantation periods. Activation o f perivascular macrophages and extravasation of ED1+ cells at the site of injury was evident by 1 day postimplantation. Macrophages were found at the implant-tissue interface at all time points and were most prevalent at 3 days. At as early as 1 day, GFAP+ astrocytes were absent from the implantation site to about 50 |im, which was maintained at days 3 and 7. There was a significant decrease in neuronal soma within 0-50 jiin of the electrode track for stab wound and implanted animals. However for implanted animals, the area of neuronal loss had increased to 0150 |itn at 7 days, suggesting that secondary neuronal cell death is part of the early phase of the foreign body response. Future studies may use pharmacological approaches to understand if these early events can be modulated to improve the longterm functionality o f microelectrodes for neuroprosthetic devices
