Electroceuticals for Regeneration of Long Nerve Gap Using Biodegradable Conductive Conduits and Implantable Wireless Stimulator.

Regeneration of over 10 mm long peripheral nerve defects remains a challenge due to the failure of regeneration by prolonged axotomy and denervation occurring in long-term recovery. Recent studies reveal that conductive conduits and electrical stimulation accelerate the regeneration of long nerve defects. In this study, an electroceutical platform combining a fully biodegradable conductive nerve conduit and a wireless electrical stimulator is proposed to maximize the therapeutic effect on nerve regeneration. Fully biodegradable nerve conduit fabricated using molybdenum (Mo) microparticles and polycaprolactone (PCL) can eliminate the unwanted effects of non-degradable implants, which occupy nerve paths and need to be removed through surgery increasing the risk of complications. The electrical and mechanical properties of Mo/PCL conduits are optimized by controlling the amounts of Mo and tetraglycol lubricant. The dissolution behavior and electrical conductivity of biodegradable nerve conduits in the biomimetic solutions are also evaluated. In in vivo experiments, the integrated strategy of a conductive Mo/PCL conduit with controlled therapeutic electrical stimulation shows accelerated axon regeneration for long sciatic nerve defects in rats compared to the use of the Mo/PCL conduit without stimulation and has a significant therapeutic effect based on the results obtained from the functional recovery test.

Ascorbic Acid Promotes Functional Restoration after Spinal Cord Injury Partly by Epigenetic Modulation.

Axonal regeneration after spinal cord injury (SCI) is difficult to achieve, and no fundamental treatment can be applied in clinical settings. DNA methylation has been suggested to play a role in regeneration capacity and neuronal growth after SCI by controlling the expression of regeneration-associated genes (RAGs). The aim of this study was to examine changes in neuronal DNA methylation status after SCI and to determine whether modulation of DNA methylation with ascorbic acid can enhance neuronal regeneration or functional restoration after SCI. Changes in epigenetic marks (5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC)); the expression of Ten-eleven translocation (Tet) family genes; and the expression of genes related to inflammation, regeneration, and degeneration in the brain motor cortex were determined following SCI. The 5hmC level within the brain was increased after SCI, especially in the acute and subacute stages, and the mRNA levels of Tet gene family members (Tet1, Tet2, and Tet3) were also increased. Administration of ascorbic acid (100 mg/kg) to SCI rats enhanced 5hmC levels; increased the expression of the Tet1, Tet2, and Tet3 genes within the brain motor cortex; promoted axonal sprouting within the lesion cavity of the spinal cord; and enhanced recovery of locomotor function until 12 weeks. In conclusion, we found that epigenetic status in the brain motor cortex is changed after SCI and that epigenetic modulation using ascorbic acid may contribute to functional recovery after SCI.

Isolated median sensory neuropathy after acupuncture.

A 47-year-old left-handed man presented with pain and numbness in his left thumb and index finger after acupuncture treatment on an acupoint in his left wrist. A technique of herbal acupuncture, involving the use of a needle coated with apricot seed extract, was used. Median nerve conduction study showed an absence of sensory nerve action potential in the left index finger, whereas the results were normal in all other fingers. The radial and ulnar nerves in the left thumb and ring finger, respectively, showed no abnormality. Infrared thermography of the left index finger showed severe hypothermia. The patient was diagnosed as having an isolated injury to the sensory nerve fibers of the median nerve innervating the index finger. This is the first case report of complications from an herbal acupuncture treatment, and it highlights the possibility of focal peripheral nerve injury caused by acupuncture.

Growth-associated protein-43 is elevated in the injured rat sciatic nerve after low power laser irradiation.

Low power laser irradiation (LPLI) has been used in the treatment of peripheral nerve injury. In this study, we verified its therapeutic effect on neuronal regeneration by finding elevated immunoreactivities (IRs) of growth-associated protein-43 (GAP-43), which is up-regulated during neuronal regeneration. Twenty Sprague-Dawley rats received a standardized crush injury of the sciatic nerve, mimicking the clinical situations accompanying partial axonotmesis. The injured nerve received calculated LPLI therapy immediately after injury and for 4 consecutive days thereafter. The walking movements of the animals were scored using the sciatic functional index (SFI). In the laser treated rats, the SFI level was higher in the laser treated animals at 3-4 weeks while the SFIs of the laser treated and untreated rats reached normal levels at 5 weeks after surgery. In immunocytochemical study, although GAP-43 IRs increased both in the untreated control and the LPLI treated groups after injury, the number of GAP-43 IR nerve fibers was much more increased in the LPLI group than those in the control group. The elevated numbers of GAP-43 IR nerve fibers reached a peak 3 weeks after injury, and then declined in both the untreated control and the LPLI groups at 5 weeks, with no differences in the numbers of GAP-43 IR nerve fibers of the two groups at this stage. This immunocytochemical study using GAP-43 antibody study shows for the first time that LPLI has an effect on the early stages of the nerve recovery process following sciatic nerve injury.