Normal Molecular Repair Mechanisms in Regenerative Peripheral Nerve Interfaces Allow Recording of Early Spike Activity Despite Immature Myelination

Abstract

Clinical use of neurally controlled prosthetics has advanced in recent years, but limitations still remain, including lacking fine motor control and sensory feedback. Indwelling multi-electrode arrays, cuff electrodes, and regenerative sieve electrodes have been reported to serve as peripheral neural interfaces, though long-term stability of the nerve-electrode interface has remained a formidable challenge. We recently developed a regenerative multi-electrode interface (REMI) that is able to record neural activity as early as seven days post-implantation. While this activity might represent normal neural depolarization during axonal regrowth, it can also be the result of altered nerve regeneration around the REMI. This study evaluated high-throughput expression levels of 84 genes involved in nerve injury and repair, and the histological changes that occur in parallel to this early neural activity. Animals exhibiting spike activity increased from 29% to 57% from 7 to 14 days following REMI implantation with a corresponding increase in firing rate of 113%. Two weeks after implantation, numbers of neurofilament-positive axons in the control and REMI implanted nerves were comparable, and in both cases the number of myelinated axons was low. During this time, expression levels of genes related to nerve injury and repair were similar in regenerated nerves, both in the presence or absence of the electrode array. Together, these results indicate that the early neural activity is intrinsic to the regenerating axons, and not induced by the REMI neurointerface.

Asymmetric Sensory-Motor Regeneration of Transected Peripheral Nerves Using Molecular Guidance Cues

“…The ability of transected nerves to regrow through multi-electrode arrays forming regenerative interfaces was demonstrated more than 20 years ago 18 . Using this approach, we have shown that peripheral nerves can be directed to grow through an 18-electrode array placed in the lumen of a conduit 19 , 20 . This regenerative multi-electrode interface (REMI) records single units as early as 7 days from both motor and sensory sub-modality axons from animals in which the interfaced nerves are allowed to reinnervate their original target in the skin and muscle 21 .…”

Interfaces with the peripheral nervous system for the control of a neuroprosthetic limb: a review

“…7) was designed 45 years ago and is a flat surface drilled through teflon-coated metal wires to open channels for the nerve fibers to grow through [116]. More advanced versions were constructed using flexible materials [117][118][119][120]. A recent design incorporated 64 channels in a double-layered sieve electrode in order to double interconnection density and increase spatial resolution.…”

Update on Peripheral Nerve Electrodes for Closed-Loop Neuroprosthetics

“…Two types of sieve electrodes exist, one is a flat penetrated piece of material (Figure 6 ), and the other is a scaffold which is folded into a sieve electrode (Figure 7 ). The regenerative multi-electrode array is designed by having multiple spikes similar to the USEA inside a hollow tube to allow more space and thus faster and non-obstructive regeneration of the nerve (Garde et al, 2009 ; Seifert et al, 2012 ). Regenerative electrodes have not yet been used for neuroprothetics and are in experimental phase.…”