Abstract
BackgroundTherapeutic ultrasound (US) is a promising physical therapy modality for peripheral nerve regeneration. However, it is necessary to identify the most effective US parameters and clarify the underlying mechanisms before its clinical application. The intensity of US is one of the most important parameters. However, the optimum intensity for the promotion of peripheral nerve regeneration has yet to be determined.ObjectivesTo identify the optimum intensity of US necessary for the promotion of peripheral nerve regeneration after crush injuries in rats and to clarify the underlying mechanisms of US by mRNA expression analysis.MethodsWe inflicted sciatic nerve crush injuries on adult Lewis rats and performed ultrasound irradiation using 4 different US intensities: 0 (sham stimulation), 30, 140, and 250 mW/cm2 with frequency (5 days/week) and duration (5 min/day). We evaluated peripheral nerve regeneration by quantitative real-time PCR one week after injury. Histomorphometric analyses and motor function analysis were evaluated 3 weeks after injury.ResultsUS stimulation enhanced re-myelination as well as sprouting of axons, especially at an intensity of 140 mW/cm2. mRNA expression revealed that US suppressed the expression of the inflammatory cytokines TNF and IL-6 and the axonal growth inhibitors SEMA3A and GSK3β.ConclusionsAn intensity of 140 mW/cm2 was optimal to support regeneration of the sciatic nerve after a crush injury in rats by, in part, the suppression of pro-inflammatory and nerve growth inhibitor gene expression.
Highlights
Peripheral nerves connect the central nervous system to the limbs and organs
US stimulation enhanced re-myelination as well as sprouting of axons, especially at an intensity of 140 mW/cm2. mRNA expression revealed that US suppressed the expression of the inflammatory cytokines tumor necrosis factor (TNF) and interleukin 6 (IL-6) and the axonal growth inhibitors semaphorin 3A (SEMA3A) and GSK3β
Myelinated nerve fibers were visible in all groups since peripheral nerves have a spontaneous regeneration ability following axonotmesis
Summary
Peripheral nerves connect the central nervous system to the limbs and organs. Peripheral nerves have intrinsic regenerative abilities, the repair process is slow. Interventions for peripheral nerve regeneration have been developed using tissue-engineered scaffolds and cell-based therapies [2,3]. Researchers are currently developing other approaches for peripheral nerve regeneration. It has been reported that adequate mechanical stress promotes peripheral nerve regeneration [4]. Mechanical stress may have synergistic positive effects with regenerative therapies [5,6,7]. Mechanical stress may be used to stimulate peripheral nerve regeneration during neurorehabilitation. Therapeutic ultrasound (US) is a promising physical therapy modality for peripheral nerve regeneration. The optimum intensity for the promotion of peripheral nerve regeneration has yet to be determined
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