Nerve Regeneration

nt J Neurosci. 2016 Aug;126(8):739-48. doi: 10.3109/00207454.2015.1054032. Epub 2015 May 26.

Effects of electromagnetic field (PEMF) exposure at different frequency and duration on the peripheral nerve regeneration: in vitro and in vivo study.

Hei WH1, Byun SH1, Kim JS2, Kim S3, Seo YK4, Park JC5, Kim SM1, Jahng JW6, Lee JH1,6.

Author information

1
a Department of Oral and Maxillofacial Surgery, School of Dentistry , Seoul National University , Seoul , Korea.
2
b Department of Oral and Maxillofacial Surgery, Hallum Medical School , Sacred Kangdong hospital , Seoul , Korea.
3
c Graduate School of Bio & Information Technology , Hankyong National University , Anseong-si, Kyonggi-do , Seoul , Korea.
4
d Research Institute of Biotechnology , Dongguk University , Seoul , Korea.
5
e Department of Oral Histology-Developmental Biology, School of Dentistry , Seoul National University , Seoul , Korea.
6
f Dental Research Institute , Seoul National University , Seoul , Korea.

Abstract

PURPOSE:

The purpose was to clarify the influence of frequency and exposure time of pulsed electromagnetic fields (PEMF) on the peripheral nerve regeneration.

MATERIALS AND METHODS:

Immortalized rat Schwann cells (iSCs) (1 × 10(2)/well) were exposed at four different conditions in 1 mT (50 Hz 1 h/d, 50 Hz 12 h/d, 150 Hz 1 h/d and 150 Hz 12h/d). Cell proliferation, mRNA expression of S100 and brain-derived neurotrophic factor (BDNF) were analyzed. Sprague-Dawley rats (200-250 g) were divided into six groups (n = 10 each): control, sham, 50 Hz 1 h/d, 50 Hz 12 h/d, 150 Hz 1 h/d and 150 Hz 12 Hr/d. Mental nerve was crush-injured and exposed at four different conditions in 1 mT (50 Hz 1 Hr/d, 50 Hz 12 Hr/d, 150 Hz 1 h/d and 150 Hz 12 h/d). Nerve regeneration was evaluated with functional test, histomorphometry and retrograde labeling of trigeminal ganglion.

RESULTS:

iSCs proliferation with 50 Hz, 1 h/d was increased from fourth to seventh day; mRNA expression of S100 and BDNF was significantly increased at the same condition from first week to third week (p < .05 vs. control); difference score was increased at the second and third week, and gap score was increased at the third under 50 Hz 1 h PEMF compared with control while other conditions showed no statistical meaning. Axon counts and retrograde labeled neurons were significantly increased under PEMF of four different conditions compared with control. Although there was no statistical difference, 50 Hz, 1 h PEMF showed highest regeneration ability than other conditions.

CONCLUSION:

PEMF enhanced peripheral nerve regeneration, and that it may be due to cell proliferation and increase in BDNF and S100 gene expression.

J Phys Ther Sci. 2014 Sep;26(9):1355-61. doi: 10.1589/jpts.26.1355. Epub 2014 Sep 17.

Effects of pulsed electromagnetic field and swimming exercise on rats with experimental sciatic nerve injury.

Kavlak E1, Belge F2, Unsal C2, Uner AG2, Cavlak U1, Cömlekçi S3.

Author information

  • 1School of Physical Therapy and Rehabilitation, Pamukkale University, Turkey.
  • 2Department of Physiology, Faculty of Veterinary Medicine, Adnan Menderes University, Turkey.
  • 3Department of Electronics and Communication, Faculty of Engineering, Süleyman Demirel University, Turkey.

Abstract

[Purpose] The current study aimed to reveal the therapeutic effects of a pulsed electromagnetic field and swimming exercises on rats with experimental sciatic nerve injury, which was induced with crush-type neuropathy model damage, using electrophysiological methods.

[Subjects] In the current study, the sample consisted of 28 adult male Wistar albino rats. [Methods] The rats were randomized into four groups (n=7). Swimming exercise and PEMF (2?Hz and 0.3 MT) were applied one hour a day, five days a week, for four weeks. Electroneuromyographic (ENMG) measurements were taken on day 7.

[Results] When the data were evaluated, it was found that the 4 weeks of PEMF and swimming exercises led to an increase in motor conduction rates and a decrease in latency values, but the changes were not significant in comparison with the control and injury groups. The compound muscle action potential (CMAP) values of the left leg were lower in weeks 2, 3, and 4 in the swimming exercise group in comparison with the control group, although for the PEMF group, the CMAP values of the left leg reached the level observed in the control group beginning in week 3.

[Conclusion] PEMF and swimming exercise made positive contributions to nerve regeneration after week 1, and regeneration was enhanced.

Int J Neurosci. 2015;125(10):774-83. doi: 10.3109/00207454.2014.971121. Epub 2014 Oct 31.

Co-treatment effect of pulsed electromagnetic field (PEMF) with human dental pulp stromal cells and FK506 on the regeneration of crush injured rat sciatic nerve.

Kim YT1, Hei WH, Kim S, Seo YK, Kim SM, Jahng JW, Lee JH.

Author information

Abstract

PURPOSE:

The purpose of this study was to determine whether crush injured rat sciatic nerve could be benefit from pulsed electromagnetic field (PEMF) combined with human dental pulp stromal cells (hDPSCs), with FK506 (Tacrolimus) for immune suppression and neuropromotion.

MATERIALS AND METHODS:

Male Sprague-Dawley rats (200-250 g, 6 week old) were distributed into 6 groups (n = 18 each): control, PEMF, FK506, PEMF + hDPSCs, PEMF + FK506, and PEMF + hDPSCs + FK506 groups. hDPSCs (cell = 1 × 106/10 ?l/rat) were injected at the crush site immediate after injury. FK506 was administered 3 weeks in FK506 group (0.5 mg/kg/d) while pre-op 1 d and post-op 7 d in PEMF + FK506 and PEMF + hDPSCs + FK506 group; cell tracking was done with PKH26-labeled hDPSCs (cell = 1 × 106/10 ?l/rat). The rats were follow-up for 3 weeks.

RESULTS:

PEMF + FK506 and PEMF + hDPSCs + FK506 group showed a sharp increase in sciatic function index (SFI), axon counts, densities, and labeled neurons in dorsal root ganglia (DRG) than control at 3 weeks. Other three treatment groups also showed higher axon counts, densities, and labeled neurons than control. Higher axon counts and densities were found in PEMF + FK506 and PEMF + hDPSCs + FK506 groups comparing with PEMF group. Brain-derived neurotrophic factor (BDNF) mRNA expression pattern in nerve segment and DRG was almost same. Higher expression level in all the treatment groups was discovered in the follow-up period, but there was no significant difference.

CONCLUSIONS:

All treatment groups can improve regeneration of neurons following crushed injury, PEMF + FK506 and PEMF + hDPSCs + FK506 groups showed higher regeneration ability than other three groups. FK506 plays an important role during hDPSCs transplantation

Altern Ther Health Med. 2006 Sep-Oct;12(5):42-9

Regenerative effects of pulsed magnetic field on injured peripheral nerves.

  • Mert T,
  • Gunay I,
  • Gocmen C,
  • Kaya M,
  • Polat S.

Department of Biophysics, University of Cukurova School of Medicine, Adana, Turkey.

Previous studies confirm that pulsed magnetic field (PMF) accelerates functional recovery after a nerve crush lesion. The contention that PMF enhances the regeneration is still controversial, however. The influence of a new PMF application protocol (trained PMF) on nerve regeneration was studied in a model of crush injury of the sciatic nerve of rats. To determine if exposure to PMF influences regeneration, we used electrophysiological recordings and ultrastructural examinations. After the measurements of conduction velocity, the sucrose-gap method was used to record compound action potentials (CAPs) from sciatic nerves. PMF treatment during the 38 days following the crush injury enhanced the regeneration. Although the axonal ultrastructures were generally normal, slight to moderate myelin sheath degeneration was noted at the lesion site. PMF application for 38 days accelerated nerve conduction velocity, increased CAP amplitude and decreased the time to peak of the CAP. Furthermore, corrective effects of PMF on. the abnormal characteristics of sensory nerve fibers were determined. Consequently, long-periodic trained-PMF may promote both morphological and electrophysiological properties of the injured nerves. In addition, corrective effects of PMF on sensory fibers may be considered an important finding for neuropathic pain therapy.

Spine. 2003 Dec 15;28(24):2660-6.

Exposure to pulsed magnetic fields enhances motor recovery in cats after spinal cord injury.

Crowe MJ, Sun ZP, Battocletti JH, Macias MY, Pintar FA, Maiman DJ.

Neuroscience Research Laboratories, The Clement J. Zablocki VA Medical Center, Milwaukee, WI 53295, USA. mcrowe@mcw.edu

STUDY DESIGN: Animal model study of eight healthy commercial cats was conducted.

OBJECTIVE: To determine whether pulsed electromagnetic field (PMF) stimulation results in improvement of function after contusive spinal cord injury in cats.

SUMMARY OF BACKGROUND DATA: PMF stimulation has been shown to enhance nerve growth, regeneration, and functional recovery of peripheral nerves. Little research has been performed examining the effects of PMF stimulation on the central nervous system and no studies of PMF effects on in vivo spinal cord injury (SCI) models have been reported.

MATERIALS AND METHODS: PMF stimulation was noninvasively applied for up to 12 weeks to the midthoracic spine of cats with acute contusive spinal cord injury. The injury was produced using a weight-drop apparatus. Motor functions were evaluated with the modified Tarlov assessment scale. Morphologic analyses of the injury sites and somatosensory-evoked potential measurements were conducted to compare results between PMF-stimulated and control groups.

RESULTS: There was a significant difference in locomotor recovery between the PMF-stimulated and control groups. Although not statistically significant, PMF-stimulated spinal cords demonstrated greater sparing of peripheral white matter and smaller lesion volumes compared to controls. Somatosensory-evoked potential measurements indicated that the PMF-stimulated group had better recovery of preinjury waveforms than the control group; however, this observation also was not statistically significant because of the small sample size.

CONCLUSIONS: This preliminary study indicates that pulsed magnetic fields may have beneficial effects on motor function recovery and lesion volume size after acute spinal cord injury.

J Neurosci Res. 1999 Jan 15;55(2):230-7.

Electromagnetic fields influence NGF activity and levels following sciatic nerve transection.

Longo FM, Yang T, Hamilton S, Hyde JF, Walker J, Jennes L, Stach R, Sisken BF.

Department of Neurology, UCSF/VAMC, San Francisco, California, USA. LFM@itsa.UCSF.edu

Pulsed electromagnetic fields (PEMF) have been shown to increase the rate of nerve regeneration. Transient post-transection loss of target-derived nerve growth factor (NGF) is one mechanism proposed to signal induction of early nerve regenerative events. We tested the hypothesis that PEMF alter levels of NGF activity and protein in injured nerve and/or dorsal root ganglia (DRG) during the first stages of regeneration (6-72 hr). Rats with a transection injury to the midthigh portion of the sciatic nerve on one side were exposed to PEMF or sham control PEMF for 4 hr/day for different time periods. NGF-like activity was determined in DRG, in 5-mm nerve segments proximal and distal to the transection site and in a corresponding 5-mm segment of the contralateral nonoperated nerve. NGF-like activity of coded tissue samples was measured in a blinded fashion using the chick DRG sensory neuron bioassay. Overall, PEMF caused a significant decrease in NGF-like activity in nerve tissue (P < 0.02, repeated measures analysis of variance, ANOVA) with decreases evident in proximal, distal, and contralateral nonoperated nerve. Unexpectedly, transection was also found to cause a significant (P=0.001) 2-fold increase in DRG NGF-like activity between 6 and 24 hr postinjury in contralateral but not ipsilateral DRG. PEMF also reduced NGF-like activity in DRG, although this decrease did not reach statistical significance. Assessment of the same nerve and DRG samples using ELISA and NGF-specific antibodies confirmed an overall significant (P < 0.001) decrease in NGF levels in PEMF-treated nerve tissue, while no decrease was detected in DRG or in nerve samples harvested from PEMF-treated uninjured rats. These findings demonstrate that PEMF can affect growth factor activity and levels, and raise the possibility that PEMF might promote nerve regeneration by amplifying the early postinjury decline in NGF activity.

Neurosci Behav Physiol. 1998 Sep-Oct;28(5):594-7.

Magnetic and electrical stimulation in the rehabilitative treatment of patients with organic lesions of the nervous system.

Tyshkevich TG, Nikitina VV.

A. L. Polenov Russian Science Research Neurosurgical Institute, St. Petersburg.

Studies were performed on 89 patients with organic lesions of the nervous system in which the leading clinical symptoms consisted of paralysis and pareses. Patients received complex treatment, including pulsed magnetic fields and an electrical stimulation regime producing multilevel stimulation. A control group of 49 patients with similar conditions was included, and these patients received only sinusoidal currents. Combined treatment with magnetic and electrical stimulation was more effective, as indicated by radiographic and electromyographic investigations.

Arch Otolaryngol Head Neck Surg. 1998 Apr;124(4):383-9.

Effect of pulsed electromagnetic stimulation on facial nerve regeneration.

Byers JM, Clark KF, Thompson GC.

Department of Otorhinolaryngology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.

OBJECTIVE: To determine if exposure to electromagnetic fields influences regeneration of the transected facial nerve in the rat.

DESIGN AND METHODS: The left facial nerve was transected in the tympanic section of the fallopian canal in 24 rats randomly assigned to 2 groups. The cut ends of the facial nerve were reapproximated without sutures within the fallopian canal to maximize the potential for regeneration. Rats in the experimental group (n= 12) were then exposed to pulsed electromagnetic stimulation (0.4 millitesla at 120 Hz) for 4 hours per day, 5 days per week, for 8 weeks. Rats in the control group (n=12) were handled in an identical manner without pulsed electromagnetic stimulation. Four other rats were given sham operations in which all surgical procedures were carried out except for the actual nerve transection. Two of these rats were placed in each group. Nerve regeneration was evaluated using electroneurography (compound action potentials), force of whisker and eyelid movements, and voluntary facial movements before and at 2-week intervals after transection. Histological evaluation was performed at 10 weeks after transection. Each dependent variable was analyzed using a 2-way analysis of variance with 1 between variable (groups) and 1 within repeated measures variable (days after transection).

RESULTS: Statistical analysis indicated that N1 (the negative deflection of depolarization phase of the muscle and/or nerve fibers) area, N1 amplitude, and N1 duration, as well as absolute amplitude of the compound action potentials, were all significantly greater 2 weeks after transection in the experimental than in the control group of rats. The force of eye and whisker movements after electrical stimulation was statistically greater in the experimental group of rats 4 weeks after transection. Voluntary eye movements in the experimental group were significantly better at 5 and 10 weeks, while whisker movements were better at 3 and 10 weeks. There was no statistical difference between the 2 groups for any histological variable.

CONCLUSION: Results of this study indicate that pulsed electromagnetic stimulation enhances early regeneration of the transected facial nerve in rats.

J Cell Biochem. 1993 Apr;51(4):387-93.

Beneficial effects of electromagnetic fields.

Bassett CA.

Bioelectric Research Center, Columbia University, Riverdale, New York 10463.

Selective control of cell function by applying specifically configured, weak, time-varying magnetic fields has added a new, exciting dimension to biology and medicine. Field parameters for therapeutic, pulsed electromagnetic field (PEMFs) were designed to induce voltages similar to those produced, normally, during dynamic mechanical deformation of connective tissues. As a result, a wide variety of challenging musculoskeletal disorders have been treated successfully over the past two decades. More than a quarter million patients with chronically ununited fractures have benefitted, worldwide, from this surgically non-invasive method, without risk, discomfort, or the high costs of operative repair. Many of the athermal bioresponses, at the cellular and subcellular levels, have been identified and found appropriate to correct or modify the pathologic processes for which PEMFs have been used. Not only is efficacy supported by these basic studies but by a number of double-blind trials. As understanding of mechanisms expands, specific requirements for field energetics are being defined and the range of treatable ills broadened. These include nerve regeneration, wound healing, graft behavior, diabetes, and myocardial and cerebral ischemia (heart attack and stroke), among other conditions. Preliminary data even suggest possible benefits in controlling malignancy.

Bioelectromagnetics. 1993;14(4):353-9.

Pretreatment of rats with pulsed electromagnetic fields enhances regeneration of the sciatic nerve.

Kanje M, Rusovan A, Sisken B, Lundborg G.

Department of Animal Physiology, University of Lund, Sweden.

Regeneration of the sciatic nerve was studied in rats pretreated in a pulsed electromagnetic field (PEMF). The rats were exposed between a pair of Helmholtz coils at a pulse repetition rate of 2 pps at a field density of 60 or 300 microT. The PEMF treatment was then discontinued. After an interval of recovery, regeneration of the sciatic nerve was initiated by a crush lesion. Regeneration of sensory fibers was measured by the “pinch test” after an additional 3-6 days. A variety of PEMF pretreatments including 4 h/day for 1-4 days or exposure for 15 min/day during 2 days resulted in an increased regeneration distance, measured 3 days after the crush lesion. This effect could be demonstrated even after a 14-day recovery period. In contrast, pretreatment for 4 h/day for 2 days at 60 microT did not affect the regeneration distance. The results showed that PEMF pretreatment conditioned the rat sciatic nerve in a manner similar to that which occurs after a crush lesion, which indicates that PEMF affects the neuronal cell body. However, the mechanism of this effect remains obscure.

Brain Res. 1989 Apr 24;485(2):309-16.

Stimulation of rat sciatic nerve regeneration with pulsed electromagnetic fields.

Sisken BF, Kanje M, Lundborg G, Herbst E, Kurtz W.

Center for Biomedical Engineering, University of Kentucky, Lexington 40506.

The effects of pulsed electromagnetic fields (PEMF) on rat sciatic nerve regeneration after a crush lesion were determined. The rats were placed between a pair of Helmholtz coils and exposed to PEMF of frequency 2 Hz and magnetic flux density of 0.3 mT. A 4 h/day treatment for 3-6 days increased the rate of nerve regeneration by 22%. This stimulatory effect was independent of the orientation of the coils. Exposure times of 1 h/day-10 h/day were equally effective in stimulating nerve regeneration. Rats exposed to PEMF for 4 h/day for 7 days before crush, followed by 3 days after crush without PEMF, also showed significantly increased regeneration. This pre-exposure ‘conditioning’ effect suggests that PEMF influences regeneration indirectly.

J Hand Surg [Br]. 1984 Jun;9(2):105-12.

An experimental study of the effects of pulsed electromagnetic field (Diapulse) on nerve repair.

Raji AM.

This study investigates the effects of a pulsed electromagnetic field (PEMF) (Diapulse) on experimentally divided and sutured common peroneal nerves in rats. Evidence is presented to show that PEMF accelerates recovery of use of the injured limb and enhances regeneration of damaged nerves.

Clin Orthop Relat Res. 1983 Dec;(181):283-90.

Effect of weak, pulsing electromagnetic fields on neural regeneration in the rat.

Ito H, Bassett CA.

The short- and long-term effects of pulsed electromagnetic fields (PEMFs) on the rate and quality of peripheral nerve regeneration were studied. High bilateral transections of rat sciatic nerves were surgically approximated (a 1-mm gap was left) and shielded with a Silastic sleeve. Animals were exposed to PEMFs for two to 14 weeks after operation. Three groups of 20 rats each (control rats and rats undergoing 12- and 24-hour/day PEMF exposure) were killed at two weeks. Histologically, regenerating axons had penetrated the distal stump nearly twice as far in the PEMF-exposed animals as in the control animals. Return of motor function was judged two to 14 weeks after operation by the load cell-measured, plantar-flexion force produced by neural stimulation proximal to the transection site. Motor function returned earlier in experimental rats and to significantly higher load levels than in control rats. Nerves from animals functioning 12-14 weeks after operation had less interaxonal collagen, more fiber-containing axis cylinders, and larger fiber diameters in the PEMF-exposed group than in the control rats. Histologic and functional data indicate that PEMFs improve the rate and quality of peripheral nerve regeneration in the severed rat sciatic nerve by a factor of approximately two.

Paraplegia. 1976 May;14(1):12-20.

Experimental regeneration in peripheral nerves and the spinal cord in laboratory animals exposed to a pulsed electromagnetic field.

Wilson DH, Jagadeesh P.

Peripheral nerve section and suture was performed in 132 rats. Postoperatively half the animals were exposed to a pulsed electromagnetic field each day and half were kept as controls. Nerve conduction studies, histology and nerve fibre counts all indicated an increased rate of regeneration in the treated animals. A similar controlled study of spinal cord regeneration following hemicordotomy in cats has been started, and preliminary results indicate that when the animals are sacrificed three months after the hemicordotomy, the pulsed electromagnetic therapy has induced nerve fibre regeneration across the region of the scar.