Microelectrode arrays offer the potential to record from and stimulate nervous tissue for the control of prosthetic devices. Such arrays may be implanted into either the central or peripheral nervous systems. While recent studies with penetrating arrays have focused on implantation in cortical targets, similar studies in the peripheral nervous system are limited. Here we used a quantitative approach to describe the foreign body response surrounding implanted Utah electrode arrays into the sciatic nerve of cats with indwelling times ranging from 36-350 days. Animals were sacrificed by transcardial perfusion with PBS followed by 4% paraformaldehyde in PBS. The sciatic nerves were isolated and the main sciatic trunk was measured using digital calipers. Based on the measurements, cross-sectional areas were estimated at 1 cm intervals from the bifurcation. Nerves sections were harvested at 1 cm proximal and distal to the implant and post fixed in 4% paraformaldehyde and 2% glutaraldehyde, followed by 2% OsO4, dehydrated in a graded series of EtOH, embedded in epon, and thin sectioned with a glass knife to 0.5-1 micron. Serial sections were stained with thionin and acridine orange. Sections were imaged using a 100x oil objective by capturing overlapping, serial fields of an entire fascicle. Fascicles were reconstructed using the photomerge command in Adobe Photoshop. Morphometric parameters, including fiber diameter and the g-ratio (radius of axon over total fiber radius), were calculated using ImagePro Plus. Gross measurements showed enlargement of the implanted nerve compared to the unimplanted side. Myelinated fiber diameter distribution showed a shift towards smaller diameter fibers while g-ratio distributions showed no particular trend verses indwelling time. A significant number of myelinated fibers were observed at all indwelling times above and below the implant site. The presence of activated macrophages in the endoneurial space also was observed at all time points. We observed a pronounced foreign body reaction in the epineurial space adjacent to the silicone containment system used, including macrophages and the formation of foreign body giant cells. This study reveals that penetrating microelectrode arrays in peripheral nerves of cats support a significant number of myelinated fibers, lead to changes in the composition of nerve fascicles, and elicit a chronic foreign body response that is characterized by persistent inflammation and some neuronal loss that is not resolved within the first year following implantation.

Support Contributed By funds from DARPA