Abstract
The purpose of this study was to evaluate whether 1 mA of percutaneous electrical stimulation (ES) at 0, 2, 20, or 200 Hz augments regeneration between the proximal and distal nerve stumps in streptozotocin diabetic rats. A10-mm gap was made in the diabetic rat sciatic nerve by suturing the stumps into silicone rubber tubes. Normal animals were used as the controls. Starting 1 week after transection, ES was applied between the cathode placed at the distal stump and the anode at the proximal stump every other day for 3 weeks. At 4 weeks after surgery, the normal controls and the groups receiving ES at 20, and 200 Hz had a higher success percentage of regeneration compared to the ES groups at 0 and 2 Hz. In addition, quantitative histology of the successfully regenerated nerves revealed that the groups receiving ES at a higher frequency, especially at 200 Hz, had a more mature structure with more myelinated fibers compared to those in the lower-frequency ES groups. Similarly, electrophysiology in the ES group at 200 Hz showed significantly shorter latency, larger amplitude, larger area of evoked muscle action potentials and faster conduction velocity compared to other groups. Immunohistochemical staining showed that ES at a higher frequency could significantly promote calcitonin gene-related peptide expression in lamina I-II regions in the dorsal horn and recruit a higher number of macrophages in the diabetic distal sciatic nerve. The macrophages were found that they could stimulate the secretion of nerve growth factor, platelet-derived growth factor, and transforming growth factor-β in dissected sciatic nerve segments. The ES at a higher frequency could also increase cutaneous blood flow in the ipsilateral hindpaw to the injury. These results indicated that a high-frequency ES could be necessary to heal severed diabetic peripheral nerve with a long gap to be repaired.
Highlights
Peripheral diabetic neuropathy leads to irreversible disability through axonal atrophy and progressive loss of axons
Since the macrophages have been considered a vital role in peripheral nerve regeneration mainly because they are profoundly involved in regulating the expression of neurotrophic factors by releasing interleukin-1 (IL-1) [7,8], we studied the changes of mRNA levels of fibroblast growth factor (FGF), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and transforming growth factor-b (TGF-b) of rat sciatic nerve segments by adding conditioned media of recombinant rat IL-1b to elucidate mechanisms underlying the observed electrical stimulation (ES) effects at different frequencies
It was noted that the ES at 200 Hz triggered a higher increase in blood flow compared to that observed at 0, 2, and 20 Hz, especially at 7 d of post-surgery that all of the differences reached the significance at p,0.05
Summary
Peripheral diabetic neuropathy leads to irreversible disability through axonal atrophy and progressive loss of axons. Until now, it is still a big challenge of how to promote regeneration of diabetic peripheral nerve. Streptozotocin (STZ)-induced rats typically have been examined in studies of diabetic peripheral nerve regeneration. Results obtained from such studies commonly showed a delay in the onset of regeneration after nerve injury that later influences the elongation, myelination, and maturation of axonal sprouts [1]. Since the macrophages have been considered a vital role in peripheral nerve regeneration mainly because they are profoundly involved in regulating the expression of neurotrophic factors by releasing interleukin-1 (IL-1) [7,8], we studied the changes of mRNA levels of fibroblast growth factor (FGF), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and transforming growth factor-b (TGF-b) of rat sciatic nerve segments by adding conditioned media of recombinant rat IL-1b to elucidate mechanisms underlying the observed ES effects at different frequencies
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