Electrical stimulation accelerates Wallerian degeneration and promotes nerve regeneration after sciatic nerve injury

Abstract

Following peripheral nerve injury (PNI), Wallerian degeneration (WD) in the distal stump can generate a microenvironment favorable for nerve regeneration. Brief low‐frequency electrical stimulation (ES) is an effective treatment for PNI, but the mechanism underlying its effect on WD remains unclear. Therefore, we hypothesized that ES could enhance nerve regeneration by accelerating WD. To verify this hypothesis, we used a rat model of sciatic nerve transection and provided ES at the distal stump of the injured nerve. The injured nerve was then evaluated after 1, 4, 7, 14 and 21 days post injury (dpi). The results showed that ES significantly promoted the degeneration and clearance of axons and myelin, and the dedifferentiation of Schwann cells. It upregulated the expression of BDNF and NGF and increased the number of monocytes and macrophages. Through transcriptome sequencing, we systematically investigated the effect of ES on the molecular processes involved in WD at 4 dpi. Evaluation of nerves bridged using silicone tubing after transection showed that ES accelerated early axonal and vascular regeneration while delaying gastrocnemius atrophy. These results demonstrate that ES promotes nerve regeneration by accelerating WD and upregulating the expression of neurotrophic factors.

Schwann cell‐specific RhoA knockout accelerates peripheral nerve regeneration via promoting Schwann cell dedifferentiation

“…Wallerian degeneration in the injured nerve plays a vital role in creating favorable microenvironment for nerve regeneration (Li et al, 2022). It is well known that both macrophages and Schwann cells can engulf the axonal and myelin debris.…”

“…Moreover, RhoA plays roles in Schwann cells differentiation through the JNK pathway, while affecting Schwann cells proliferation by regulating the AKT pathway (Tan et al, 2018; Wen et al, 2018; Wen, Qian, et al, 2017). After nerve injury, Schwann cells dedifferentiate and transform into the repair phenotype, which can clear the debris of axons and myelin to accelerate Wallerian degeneration, and secrete neurotrophins to enhance nerve regeneration (Jessen & Mirsky, 2016; Klimovich et al, 2021; Li et al, 2022). Until now, the role of RhoA in Schwann cells for nerve injury and regeneration has not been reported yet.…”

Global research trends and hotspots of artificial intelligence research in spinal cord neural injury and restoration—a bibliometrics and visualization analysis

“… Neuromodulation and noninvasive electrical stimulation: the cluster analysis of literature co-citations and literature co-citations in the last 5 years shows that neuromodulation and noninvasive electrical stimulation are continuing hotspots in this field. Neuroelectrical stimulation is a noninvasive stimulation strategy ( 32 ) that transforms neuronal networks from dormant to functional, thereby gradually restoring control over paralyzed muscles ( 33 , 34 ). In this regard, “numerical models” enhanced by deep learning algorithms are the basis for theoretical simulations of neurostimulation techniques and provide technical guidance for clinical applications.…”

Emerging role of extracellular vesicles and exogenous stimuli in molecular mechanisms of peripheral nerve regeneration

“…Thus, the reported optimal parameters for ES are an intensity of 100 mV/mm ES and a duration of 1 h ( Hu et al, 2019 ). Concerning SC stimulation, Koppes et al found that electrically stimulating SCs at a frequency of 20 Hz (with pulses of 100 μs at 3 V) in an electrotaxis setup led to the overexpression of growth-associated protein (GAP)-43, ɑ1-tubulin, and TrkB, all of which contribute to axonal outgrowth and nerve regeneration ( English et al, 2007 ; Geremia et al, 2007 ; Koppes et al, 2014 ; Li et al, 2023 ).…”