Peripheral nerve injury (PNI) usually leads to progressive muscle atrophy and poor functional recovery. Previous studies have demonstrated that non-coding ribonucleic acid (ncRNA) is a key regulator of muscle atrophy and beneficial for the treatment of PNI. We aimed to analyze the whole transcriptome involved in denervated muscle atrophy after PNI. Animal models of sciatic nerve injury were assessed at 0 (control group), 1, 2, 4, and 8 weeks after injury. The expression patterns in the whole transcriptome in the gastrocnemius muscle were profiled using RNA sequencing at each time point and compared to that obtained in the control group. Six-hundred and sixty-four long non-coding RNAs, 671 microRNAs, 236 circular RNAs, and 12,768 messenger RNAs (mRNAs) were differentially expressed (DE) after injury. Changes in some of the DE ncRNAs and mRNAs were validated using quantitative polymerase chain reaction. Gene Ontology and Kyoko Encyclopedia of Genes and Genomes analysis revealed the potential functions of and relationships among the DE ncRNAs and mRNAs. To our knowledge, this is the first study to expound the whole transcriptome involved in denervated muscle atrophy, and provides a theoretical basis for further research targeting ncRNAs.

Electrical stimulation (ES) has been proven to be an effective means of enhancing the speed and accuracy of nerve regeneration. However, these results were recorded when the procedure was performed almost immediately after nerve injury. In clinical settings, most patients cannot be treated immediately. Some patients with serious trauma or contaminated wounds need to wait for nerve repair surgery. Delays in nerve repair have been shown to be associated with poorer results than immediate surgery. It is not clear whether electrical stimulation still has any effect on nerve regeneration after enough time has elapsed. A delayed nerve repair model in which the rats received delayed nerve repair after 1 day, 1 week, 1 month, and 2 months was designed. At each point in time, the nerve stumps of half the rats were bridged with an absorbable conduit and the rats were given 1 h of weak electrical stimulation. The other half was not treated. In order to analyze the morphological and molecular differences among these groups, 6 ES rats and 6 sham ES rats per point in time were killed 5 days after surgery. The other rats in each group were allowed to recover for 6 weeks before the final functional test and tissue observation. The amounts of myelinated fibers in the distal nerve stumps decreased as the delay in repair increased for both ES rats and sham ES rats. In the 1-day-delay and 1-week-delay groups, there were more fibers in ES rats than in sham ES rats. And the compound muscle action potential (CMAP) and motor nerve conduction velocity (MNCV) results were better for ES rats in these two groups. In order to analyze the mechanisms underlying these differences, Masson staining was performed on the distal nerves and quantitative PCR on the spinal cords. Results showed that, after delays in repair of 1 month and 2 months, there was more collagen tissue hyperplasia in the distal nerve in all rats. The brain-derived neurotrophic factor (BDNF) and trkB expression levels in the spinal cords of ES rats were higher than in sham ES rats. However, these differences decreased as the delay in repair increased. Electrical stimulation does not continue to promote nerve regeneration after long delays in nerve repair. The effective interval for nerve regeneration after delayed repair was found to be less than 1 month. The mechanism seemed to be related to the expression of nerve growth factors and regeneration environment in the distal nerves.

Epineurium or perineurium neurorrhaphy to recover the nerve continuity was the choice of peripheral nerve mutilation. The nerve selective regeneration theory was put forth by Cajal et al. As this theory was gradually accepted, many researchers had focused on it and its possible application. Our labs had centered on the small gap sleeve bridging fields for about 30 years, using autogeneic vein, artery and biogradable chitin conduits. Our goal was to improve the nerve regeneration effect by means of nerve selective regeneration theory and degradable biomaterials. This serial experiment was to confirm the possibilities of using conduit small gap sleeve bridging to substitute the traditional epineurium neurorrhaphy.

Nerve regeneration and re-innervation are usually difficult after peripheral nerve injury. Epineurium neurorrhaphy to recover the nerve continuity is the traditional choice of peripheral nerve mutilation without nerve defects, whereas the functional recovery remains quite unsatisfactory. Based on previous research in SD rats and Rhesus Monkeys, a multiple centers clinical trial about biodegradable conduit small gap tubulization for peripheral nerve mutilation to substitute traditional epineurial neurorrhaphy was carried out. Herein, the authors reviewed the literature that focused on peripheral nerve injury and possible clinical application, and confirmed the clinical possibilities of biodegradable conduit small gap tubulization to substitute traditional epineurial neurorrhaphy for peripheral nerve mutilation. The biodegradable conduit small gap tubulization to substitute traditional epineurial neurorrhaphy for peripheral nerve mutilation may be a revolutionary innovation in peripheral nerve injury and repair field.