Neural prostheses: electrophysiological and histological evaluation of central nervous system alterations due to long-term implants of sieve electrodes to peripheral nerves in cats.

We have investigated the alterations that the long-term implant of sieve electrodes to the peripheral nerves could evoke in the central nervous system by studying the neural activity at various levels of the somatosensory system [the implanted nerves, the dorsal column nuclei (DCN), and the primary somatosensory cortex (SI)] up to 30 months after implantation of the electrode in the distal median nerve in adult cats. This long survival period, which could correspond to 15 years within a human lifespan, enabled us to confirm the biocompatibility of the electrode. We also performed histological and molecular studies on sections of the spinal cord, DCN, and SI and electrophysiological recordings on of DCN and SI. Although in the "implanted" regions (ipsilateral nerve, ipsilateral DCN, and contralateral SI) there was apparently a good recovery of a number of molecular markers, mostly related to local metabolism and neurotransmission in central relay structures, the expression of calcium-binding proteins in the cortex, which identifies inhibitory interneurons, remained clearly abnormal, although they were never as altered as in case of irreversible, chronic denervations. Also, prominent anatomical disorganization was detected in the normal spatial arrangement of neural clusters within the DCN. With respect to the electrical activity the "implanted side" showed minor changes in response latency, intensity, and somatotopy, compared to control recordings. These findings show that central sensory-processing structures achieve fair, but not complete, levels of structural and functional reorganization following chronic intraneural implants of sieve electrodes.