Regenerative peripheral nerve interfaces for real-time, proportional control of a Neuroprosthetic hand.

INTRODUCTION: Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models has not yet been demonstrated. The purpose of this study was to: a) design and validate a system for translating electromyography (EMG) signals from an RPNI in a rat model into real-time control of a neuroprosthetic hand, and; b) use the system to demonstrate RPNI proportional neuroprosthesis control. METHODS: Animals were randomly assigned to three experimental groups: (1) Control; (2) Denervated, and; (3) RPNI. In the RPNI group, the extensor digitorum longus (EDL) muscle was dissected free, denervated, transferred to the lateral thigh and neurotized with the residual end of the transected common peroneal nerve. Rats received tactile stimuli to the hind-limb via monofilaments, and electrodes were used to record EMG. Signals were filtered, rectified and integrated using a moving sample window. Processed EMG signals (iEMG) from RPNIs were validated against Control and Denervated group outputs. RESULTS: Voluntary reflexive rat movements produced signaling that activated the prosthesis in both the Control and RPNI groups, but produced no activation in the Denervated group. Signal-to-Noise ratio between hind-limb movement and resting iEMG was 3.55 for Controls and 3.81 for RPNIs. Both Control and RPNI groups exhibited a logarithmic iEMG increase with increased monofilament pressure, allowing graded prosthetic hand speed control (R2 = 0.758 and R2 = 0.802, respectively). CONCLUSION: EMG signals were successfully acquired from RPNIs and translated into real-time neuroprosthetic control. Signal contamination from muscles adjacent to the RPNI was minimal. RPNI constructs provided reliable proportional prosthetic hand control.

Characterization of skeletal muscle effects associated with daptomycin in rats.

Daptomycin is a lipopeptide antibiotic with strong bactericidal effects against Gram-positive bacteria and minor side effects on skeletal muscles. The type and magnitude of the early effect of daptomycin on skeletal muscles of rats was quantified by histopathology, examination of contractile properties, Evans Blue Dye uptake, and effect on the patch repair process. A single dose of daptomycin of up to 200 mg/kg had no effect on muscle fibers. A dose of 150 mg/kg of daptomycin, twice per day for 3 days, produced a small number of myofibers (

Electrical stimulation prior to delayed reinnervation does not enhance recovery in muscles of rats.

PURPOSE: Prolonged denervation of skeletal muscles results in atrophy and poor recovery of motor function following delayed reinnervation. Electrical stimulation reduces denervation atrophy. We hypothesized that electrical stimulation of denervated extensor digitorum longus (EDL) muscles during a prolonged period between nerve axotomy and opportunity for reinnervation by motoneurons after nerve-repair would enhance the recovery of muscle mass, force and motor-function. METHODS: The EDL muscles of rats were denervated for 3.5 months by peroneal nerve axotomy, then repaired with an end-to-end neurorrhaphy, and allowed to recover for 6.5 months. During the period of denervation, some of the rats received a protocol of electrical stimulation that had previously been shown to dramatically attenuate the effects of denervation atrophy through 4 months. Other experimental groups included unoperated control muscles, denervated muscles, and axotomy followed immediately by nerve-repair. Final evaluations included walking track analysis, maximum force measured in situ by indirect stimulation of the nerve, and muscle mass. RESULTS: The hypothesis was not supported. Electrical stimulation during the period of denervation did not enhance recovery of muscle mass, force or motor function. CONCLUSION: The primary factors that inhibited reinnervation and recovery following delayed reinnervation were not alleviated by the electrical stimulation during the period of muscle denervation.

Electrical stimulation of denervated muscles of rats maintains mass and force, but not recovery following grafting.

PURPOSE: Denervated skeletal muscles lack contractile activity and subsequently lose mass and force generation. Prolonged periods of denervation prior to nerve-implant grafting limit the recovery of mass and force. We hypothesized that electrical stimulation during a period of denervation that maintains mass and force above the levels of denervated muscles enhances the recovery of mass and force following nerve-implant grafting. METHODS: The extensor digitorum longus (EDL) muscles of anesthetized rats were denervated, and a stimulator was implanted. Following 4 or 7 months of denervation, with or without electrical stimulation, the EDL muscles were removed, evaluated in vitro for mass and contractile properties, and then nerve-implant grafted into syngeneic rats. Unoperated, contralateral muscles were also evaluated and grafted. RESULTS: The hypothesis was not supported by the experimental data. Compared with values for 4- or 7-month denervated muscles, the stimulated-denervated muscles maintained higher mass and force, less prolonged time-to-peak tensions and half-relaxation times, and higher excitability. Nevertheless, the recovery of mass and force following grafting was not improved. CONCLUSION: The factors within long-term denervated muscles that hinder recovery following grafting appear to be related primarily to factors associated with the duration of denervation and not to the level of atrophy and weakness prior to grafting.

Number of contractions to maintain mass and force of a denervated rat muscle.

Within 5 weeks, denervated extensor digitorum longus (EDL) muscles of rats lose 66% of mass, 91% of force, and 76% of fiber cross-sectional area (CSA). We previously determined the parameters of electrical stimulation for denervated rat EDL muscles to generate tetanic contractions sufficient to maintain mass and force close to control values. Using these parameters, we tested the hypothesis that a range exists for number of contractions per day, below and above which values for mass, maximum force, and fiber CSA are lower than values for innervated control muscles. For 5 weeks, denervated EDL muscles were stimulated to generate between 25 and 5000 contractions daily with contractions separated by constant intervals of rest, repeated 24 h per day. Force was not maintained with fewer than 200 or more than 800 contractions daily, whereas mass and fiber CSA were not maintained with fewer than 50 contractions daily. Protocols of stimulation that maintain muscle mass and force during prolonged periods of denervation may minimize problems clinically associated with denervation atrophy.