The effect of charge-balanced transcutaneous electrical nerve stimulation on rodent facial nerve regeneration

Abstract

This study aimed to investigate the effect of charge-balanced transcutaneous electrical nerve stimulation (cb-TENS) in accelerating recovery of the facial function and nerve regeneration after facial nerve (FN) section in a rat model. The main trunk of the left FN was divided and immediately sutured just distal to the stylomastoid foramen in 66 Sprague–Dawley rats. The control group had no electrical stimulus. The other two groups received cb-TENS at 20 Hz (20 Hz group) or 40 Hz (40 Hz group). Cb-TENS was administered daily for seven days and then twice a week for three weeks thereafter. To assess the recovery of facial function, whisker movement was monitored for four weeks. Histopathological evaluation of nerve regeneration was performed using transmission electron microscopy (TEM) and confocal microscopy with immunofluorescence (IF) staining. In addition, the levels of various molecular biological markers that affect nerve regeneration were analyzed. Whisker movement in the cb-TENS groups showed faster and better recovery than the control group. The 40 Hz group showed significantly better movement at the first week after injury (p < 0.0125). In histopathological analyses using TEM, nerve axons and Schwann cells, which were destroyed immediately after the injury, recovered in all groups over time. However, the regeneration of the myelin sheath was remarkably rapid and thicker in the 20 Hz and 40 Hz groups than in the control group. Image analysis using IF staining showed that the expression levels of S100B and NF200 increased over time in all groups. Specifically, the expression of NF200 in the 20 Hz and 40 Hz groups increased markedly compared to the control group. The real-time polymerase chain reaction was performed on ten representative neurotrophic factors, and the levels of IL-1β and IL-6 were significantly higher in the 20 and 40 Hz groups than in the control group (p < 0.015). Cb-TENS facilitated and accelerated FN recovery in the rat model, as it significantly reduced the recovery time for the whisker movement. The histopathological study and analysis of neurotrophic factors supported the role of cb-TENS in the enhanced regeneration of the FN.

Corneal Neuro-Regenerative Effect of Transcutaneous Electrical Stimulation in Rabbit Lamellar Keratectomy Model

“…Studies of electrical stimulation with a 20-Hz frequency on the damaged facial and sciatic nerves of rats demonstrated increased BDNF expression and improved nerve structure. 50 – 52 Compared to the control group, sciatic function index and axonal density were increased by 26% and 19%, respectively, after 3 weeks of 20-Hz electrical stimulation. 52 Facial function recovered more rapidly in the 20- and 40-Hz electrical stimulation groups.…”

“… 52 Facial function recovered more rapidly in the 20- and 40-Hz electrical stimulation groups. 50 As for the muscle action potentials, the regenerated sciatic nerves treated with 2-Hz of electrical stimulation had a significantly shorter latency, longer duration, and faster nerve conductive velocity compared to the other groups (the control, 1-Hz, 20-Hz, and 200-Hz groups). 31 A 2-Hz burst pulse showed better nerve regeneration capacity than 100-Hz pulse electrical stimulation in the study by Cavalcante Miranda de Assis et al, 47 and NGF expression was maximized (4.1-fold increase) with 1-Hz electrical stimulation on cultured Schwann cells in the study by Huang et al 48 Morimoto et al reported the neuroprotective effect of 1-, 5-, and 20-Hz electrical stimulations observed from retinal ganglion cells and suggested that other parameters, such as current intensity, pulse duration, and stimulation time, have potential for different neuroprotective effects.…”

“…Although several parameters of electrical stimulation for nerve recovery have been explored, 31 , 47 – 50 the optimal parameters in peripheral nerves, including the corneal nerve, have not yet been confirmed. Studies of electrical stimulation with a 20-Hz frequency on the damaged facial and sciatic nerves of rats demonstrated increased BDNF expression and improved nerve structure.…”

Physical Cue‐Based Strategies on Peripheral Nerve Regeneration

“…Transcutaneous ES system, comprised of an extracorporeal programmable power generator (generally supply adjustable low-frequency pulse current), transcutaneous output leads, and electro-acupuncture or implanted metal-sheet electrodes has been extensively studied for the clinic treatment of PNI. [121][122][123] In that scenario, trained operators can formulate custom-tailored ES courses dependent on different patients thus achieving scheduled modulating. Exerted pulsed current incurs the change of either sides of the membrane potential difference (depolarization, positive charges on the excitable cell membrane surface are captured by the negative charges on the electrode) and consequently opening the voltage-gated calcium channels, thus allowing extracellular Ca 2+ cell physiological activity and function.…”

Effect of Electrical Stimulation on Nerve-Guided Facial Nerve Regeneration

“…14 In particular, our group found that charge-balanced transcutaneous electrical nerve stimulation (cb-TENS) using a 20 Hz pulse waveform was very effective in regenerating the FN. 15 Therefore, when the FN is unavoidably resected and direct anastomosis is impossible, using cb-TENS may be more efficient than using PLCL conduits alone. If this is proven, it has important implications not only for the FN but also for treating other damaged nerves in vivo.…”