Dermal Sensory Regenerative Peripheral Nerve Interface for Reestablishing Sensory Nerve Feedback in Peripheral Afferents in the Rat.

BACKGROUND: Without meaningful, intuitive sensory feedback, even the most advanced myoelectric devices require significant cognitive demand to control. The dermal sensory regenerative peripheral nerve interface (DS-RPNI) is a biological interface designed to establish high-fidelity sensory feedback from prosthetic limbs. METHODS: DS-RPNIs were constructed in rats by securing fascicles of residual sensory peripheral nerves into autologous dermal grafts, with the objectives of confirming regeneration of sensory afferents within DS-RPNIs and establishing the reliability of afferent neural response generation with either mechanical or electrical stimulation. RESULTS: Two months after implantation, DS-RPNIs were healthy and displayed well-vascularized dermis with organized axonal collaterals throughout and no evidence of neuroma. Electrophysiologic signals were recorded proximal from DS-RPNI's sural nerve in response to both mechanical and electrical stimuli and compared with (1) full-thickness skin, (2) deepithelialized skin, and (3) transected sural nerves without DS-RPNI. Mechanical indentation of DS-RPNIs evoked compound sensory nerve action potentials (CSNAPs) that were like those evoked during indentation of full-thickness skin. CSNAP firing rates and waveform amplitudes increased in a graded fashion with increased mechanical indentation. Electrical stimuli delivered to DS-RPNIs reliably elicited CSNAPs at low current thresholds, and CSNAPs gradually increased in amplitude with increasing stimulation current. CONCLUSIONS: These findings suggest that afferent nerve fibers successfully reinnervate DS-RPNIs, and that graded stimuli applied to DS-RPNIs produce proximal sensory afferent responses similar to those evoked from normal skin. This confirmation of graded afferent signal transduction through DS-RPNI neural interfaces validate DS-RPNI's potential role of facilitating sensation in human-machine interfacing. CLINICAL RELEVANCE STATEMENT: The DS-RPNI is a novel biotic-abiotic neural interface that allows for transduction of sensory stimuli into neural signals. It is expected to advance the restoration of natural sensation and development of sensorimotor control in prosthetics.

Regenerative peripheral nerve interface free muscle graft mass and function.

BACKGROUND: Regenerative peripheral nerve interfaces (RPNIs) transduce neural signals to provide high-fidelity control of neuroprosthetic devices. Traditionally, rat RPNIs are constructed with ~150 mg of free skeletal muscle grafts. It is unknown whether larger free muscle grafts allow RPNIs to transduce greater signal. METHODS: RPNIs were constructed by securing skeletal muscle grafts of various masses (150, 300, 600, or 1200 mg) to the divided peroneal nerve. In the control group, the peroneal nerve was transected without repair. Endpoint assessments were conducted 3 mo postoperatively. RESULTS: Compound muscle action potentials (CMAPs), maximum tetanic isometric force, and specific muscle force were significantly higher for both the 150 and 300 mg RPNI groups compared to the 600 and 1200 mg RPNIs. Larger RPNI muscle groups contained central areas lacking regenerated muscle fibers. CONCLUSIONS: Electrical signaling and tissue viability are optimal in smaller as opposed to larger RPNI constructs in a rat model.

Sumatriptan improves the locomotor activity and neuropathic pain by modulating neuroinflammation in rat model of spinal cord injury.

OBJECTIVES: To investigate the therapeutic effects of sumatriptan in a rat model of spinal cord injury (SCI) and possible anti-inflammatory and analgesic mechanisms underlying this effect. METHODS: Using an aneurysm mini-clip model of contusive SCI, T9-10 laminectomies were performed for 60 male rats. Animals were divided into six experimental groups (n = 10 per group) as follows: a minocycline administered positive control group, a saline-vehicle negative control group, a sham-operated group, and three experimental groups which received separate doses of sumatriptan (0.1, 0.3 and 1 mg/kg). Behavioural assessments were used to evaluate locomotor activity and neuropathic pain for 28 days. At the end of the study, spinal cord tissues were collected from sacrificed animals for histopathological analysis. Levels of calcitonin gene-related peptide (CGRP) and two pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-1ß) were assessed by the enzyme-linked immunosorbent assay (ELISA). RESULTS: Sumatriptan significantly (P < 0.001) improved the locomotor activity in SCI group. Sumatriptan was also more effective than the positive control, i.e. minocycline (0.3 mg/kg). Additionally, sumatriptan and minocycline similarly attenuated the mechanical and thermal allodynia in SCI (P < 0.001). TNF-α, IL-1ß and CGRP levels in sumatriptan- and minocycline-treated groups significantly (P < 0.001) decreased compared to controls. Histopathological analysis also revealed a markedly improvement in hemorrhage followed by inflammatory cell invasion, neuronal vacuolation, and cyst formation in both sumatriptan- and minocycline-treated groups compared to control animals. CONCLUSIONS: Sumatriptan improves functional recovery from SCI through its anti-inflammatory effects and reducing pro-inflammatory and pain mediators.

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.

Current State of the Surgical Treatment of Terminal Neuromas.

Painful terminal neuromas resulting from nerve injury following amputation are common. However, there is currently no universally accepted gold standard of treatment for this condition. A comprehensive literature review is presented on the treatment of terminal neuromas. Four categories of terminal neuroma surgical procedures are assessed: epineurial closure; nerve transposition with implantation; neurorrhaphy, and alternate target reinnervation. Significant patient and case studies are highlighted in each section, focusing on surgical technique and patient outcome metrics. Studies presented consisted of a PubMed search for "terminal neuromas," without year limitation. The current available research supports the use of implantation into muscle for the surgical treatment of terminal neuromas. However, this technique has several fundamental flaws that limit its utility, as it does not address the underlying physiology behind neuroma formation. Regenerative peripheral nerve interfaces and targeted muscle reinnervation are 2 techniques that seem to offer the most promise in preventing and treating terminal neuroma formation. Both techniques are also capable of generating control signals which can be used for both motor and sensory prosthetic control. Such technology has the potential to lead to the future restoration of lost limb function in amputees. Further clinical research employing larger patient groups with high-quality control groups and reproducible outcome measures is needed to determine the most effective and beneficial surgical treatment for terminal neuromas. Primary focus should be placed on investigating techniques that most closely approximate the theoretically ideal neuroma treatment, including targeted muscle reinnervation and regenerative peripheral nerve interfaces.

In vivo characterization of regenerative peripheral nerve interface function.

OBJECTIVE: Regenerative peripheral nerve interfaces (RPNIs) are neurotized free autologous muscle grafts equipped with electrodes to record myoelectric signals for prosthesis control. Viability of rat RPNI constructs have been demonstrated using evoked responses. In vivo RPNI characterization is the next critical step for assessment as a control modality for prosthetic devices. APPROACH: Two RPNIs were created in each of two rats by grafting portions of free muscle to the ends of divided peripheral nerves (peroneal in the left and tibial in the right hind limb) and placing bipolar electrodes on the graft surface. After four months, we examined in vivo electromyographic signal activity and compared these signals to muscular electromyographic signals recorded from autologous muscles in two rats serving as controls. An additional group of two rats in which the autologous muscles were denervated served to quantify cross-talk in the electrode recordings. Recordings were made while rats walked on a treadmill and a motion capture system tracked the hind limbs. Amplitude and periodicity of signals relative to gait were quantified, correlation between electromyographic and motion recording were assessed, and a decoder was trained to predict joint motion. MAIN RESULTS: Raw RPNI signals were active during walking, with amplitudes of 1 mVPP, and quiet during standing, with amplitudes less than 0.1 mVPP. RPNI signals were periodic and entrained with gait. A decoder predicted bilateral ankle motion with greater than 80% reliability. Control group signal activity agreed with literature. Denervated group signals remained quiescent throughout all evaluations. SIGNIFICANCE: In vivo myoelectric RPNI activity encodes neural activation patterns associated with gait. Signal contamination from muscles adjacent to the RPNI is minimal, as demonstrated by the low amplitude signals obtained from the Denervated group. The periodicity and entrainment to gait of RPNI recordings suggests the transduced signals were generated via central nervous system control.

Attitudes of Ghanaian women toward genetic testing for sickle cell trait.

OBJECTIVE: To explore the attitudes of Ghanaian women toward genetic testing for the sickle cell trait and to investigate key factors that promote or impede the decision to pursue knowledge of the carrier status. METHODS: A survey, administered in person to Ghanaian women, collected demographic information and information on the participants' knowledge about their carrier status, their attitudes toward genetic testing, and their perceptions of the implications of being a carrier. The results for women who had previously undergone testing and those who had not were compared. RESULTS: Of 124 participants, 75 had been tested for the sickle cell trait and 49 had not. Some 53% of the women who had been tested did not know their carrier status. Most women agreed that getting a prenatal genetic test was important. However, nontested women were more likely to lack the financial resources to undergo testing, to think that testing is futile because sickle cell disease is not curable, and to believe that the outcome of their child's health is determined by God. CONCLUSION: The women tended to have favorable attitudes toward genetic testing, but numerous barriers remained that precluded knowledge of their carrier status or the pursuit of this knowledge.