Low‑frequency pulsed electromagnetic field promotes functional recovery, reduces inflammation and oxidative stress, and enhances HSP70 expression following spinal cord injury

Wang,Chunyan; Liu,Yang; Wang,Yao; Wei,Zhijian; Suo,Dongmei; Ning,Guangzhi; Wu,Qiuli; Feng,Shiqing; Wan,Chunxiao

doi:10.3892/mmr.2019.9820

Low‑frequency pulsed electromagnetic field promotes functional recovery, reduces inflammation and oxidative stress, and enhances HSP70 expression following spinal cord injury

Authors:
- Chunyan Wang
- Yang Liu
- Yao Wang
- Zhijian Wei
- Dongmei Suo
- Guangzhi Ning
- Qiuli Wu
- Shiqing Feng
- Chunxiao Wan
View Affiliations

Affiliations: Department of Rehabilitation Medicine, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
Published online on: January 4, 2019 https://doi.org/10.3892/mmr.2019.9820
Pages: 1687-1693
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Low‑frequency pulsed electromagnetic fields (LPEMFs) have been reported to be protective for multiple diseases. However, whether the administration of LPEMFs inhibits inflammation and oxidative stress following spinal cord injury requires further investigation. In the current study, a contusion spinal cord injury model was used and LPEMFs administration was applied to investigate the molecular changes, including inflammation, oxidative stress and heat shock protein 70 (HSP70) levels. The results revealed that LPEMFs significantly promoted functional recovery following spinal cord injury, as demonstrated by an increased Basso, Beattie and Bresnahan score. The results demonstrated that LPEMFs decreased the expression of inflammatory factors, including tumor necrosis factor‑α, interleukin‑1β and nuclear factor‑κB. Additionally, LPEMFs exposure reduced the levels of inducible nitric oxide synthase and reactive oxygen species, and upregulated the expression of catalase and superoxide dismutase. Furthermore, treatment with LPEMFs significantly enhanced the expression of HSP70 in spinal cord‑injured rats. Overall, the present study revealed that LPEMFs promote functional recovery following spinal cord injury, potentially by modulating inflammation, oxidative stress and HSP70.

View Figures

View References

1	Ropper AE and Ropper AH: Acute spinal cord compression. N Eng J Med. 376:1358–1369. 2017. View Article : Google Scholar
2	Furlan JC, Sakakibara BM, Miller WC and Krassioukov AV: Global incidence and prevalence of traumatic spinal cord injury. Can J Neurol Sci. 40:456–464. 2013. View Article : Google Scholar : PubMed/NCBI
3	Jain NB, Ayers GD, Peterson EN, Harris MB, Morse L, O'Connor KC and Garshick E: Traumatic spinal cord injury in the United States, 1993–2012. JAMA. 313:2236–2243. 2015. View Article : Google Scholar : PubMed/NCBI
4	Miller LE and Herbert WG: Health and economic benefits of physical activity for patients with spinal cord injury. Clinicoecon Outcomes Res. 8:551–558. 2016. View Article : Google Scholar : PubMed/NCBI
5	Hurlbert RJ, Hadley MN, Walters BC, Aarabi B, Dhall SS, Gelb DE, Rozzelle CJ, Ryken TC and Theodore N: Pharmacological therapy for acute spinal cord injury. Neurosurgery. 72 Suppl 2:S93–S105. 2013. View Article : Google Scholar
6	Herzer KR, Chen Y, Heinemann AW and González-Fernández M: Association between time to rehabilitation and outcomes after traumatic spinal cord injury. Arch Phys Med Rehabil. 97:1620–1627.e4. 2016. View Article : Google Scholar : PubMed/NCBI
7	Anwar MA, Al Shehabi TS and Eid AH: Inflammogenesis of secondary spinal cord injury. Front Cell Neurosci. 10:982016. View Article : Google Scholar : PubMed/NCBI
8	Huang JH, Yin XM, Xu Y, Xu CC, Lin X, Ye FB, Cao Y and Lin FY: Systemic administration of exosomes released from mesenchymal stromal cells attenuates apoptosis, inflammation, and promotes angiogenesis after spinal cord injury in rats. J Neurotrauma. 34:3388–3396. 2017. View Article : Google Scholar : PubMed/NCBI
9	Xun C, Mamat M, Guo H, Mamati P, Sheng J, Zhang J, Xu T, Liang W, Cao R and Sheng W: Tocotrienol alleviates inflammation and oxidative stress in a rat model of spinal cord injury via suppression of transforming growth factor-β. Exp Ther Med. 14:431–438. 2017. View Article : Google Scholar : PubMed/NCBI
10	Zou J, Chen Y, Qian J and Yang H: Effect of a low-frequency pulsed electromagnetic field on expression and secretion of IL-1β and TNF-α in nucleus pulposus cells. J Int Med Res. 45:462–470. 2017. View Article : Google Scholar : PubMed/NCBI
11	Ehnert S, Fentz AK, Schreiner A, Birk J, Wilbrand B, Ziegler P, Reumann MK, Wang H, Falldorf K and Nussler AK: Extremely low frequency pulsed electromagnetic fields cause antioxidative defense mechanisms in human osteoblasts via induction of •O₂ and H₂O₂. Sci Rep. 7:145442017. View Article : Google Scholar : PubMed/NCBI
12	Urnukhsaikhan E, Mishig-Ochir T, Kim SC, Park JK and Seo YK: Neuroprotective effect of low frequency-pulsed electromagnetic fields in ischemic stroke. Appl Biochem Biotechnol. 181:1360–1371. 2017. View Article : Google Scholar : PubMed/NCBI
13	Capelli E, Torrisi F, Venturini L, Granato M, Fassina L, Lupo GF and Ricevuti G: Low-frequency pulsed electromagnetic field is able to modulate miRNAs in an experimental cell model of Alzheimer's disease. J Healthc Eng 2017. 25302702017.
14	Dey S, Bose S, Kumar S, Rathore R, Mathur R and Jain S: Extremely low frequency magnetic field protects injured spinal cord from the microglia- and iron-induced tissue damage. Electromagn Biol Med. 36:330–340. 2017. View Article : Google Scholar : PubMed/NCBI
15	NIH (National Institutes of Health U.S.A): Guide for the Care and Use of Laboratory Animals. The National Academies Press; Washington, DC: pp. 2462011
16	Zhou H, Li X, Wu Q, Li F, Fu Z, Liu C, Liang Z, Chu T, Wang T, Lu L, et al: shRNA against PTEN promotes neurite outgrowth of cortical neurons and functional recovery in spinal cord contusion rats. Regen Med. 10:411–429. 2015. View Article : Google Scholar : PubMed/NCBI
17	Basso DM, Beattie MS and Bresnahan JC: A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 12:1–21. 1995. View Article : Google Scholar : PubMed/NCBI
18	Wei ZJ, Zhou XH, Fan BY, Lin W, Ren YM and Feng SQ: Proteomic and bioinformatic analyses of spinal cord injury-induced skeletal muscle atrophy in rats. Mol Med Rep. 14:165–174. 2016. View Article : Google Scholar : PubMed/NCBI
19	Xu L, Botchway BOA, Zhang S, Zhou J and Liu X: Inhibition of NF-κB signaling pathway by resveratrol improves spinal cord injury. Front Neurosci. 12:6902018. View Article : Google Scholar : PubMed/NCBI
20	Ferroni L, Tocco I, De Pieri A, Menarin M, Fermi E, Piattelli A, Gardin C and Zavan B: Pulsed magnetic therapy increases osteogenic differentiation of mesenchymal stem cells only if they are pre-committed. Life Sci. 152:44–51. 2016. View Article : Google Scholar : PubMed/NCBI
21	Ottani V, De Pasquale V, Govoni P, Franchi M, Zaniol P and Ruggeri A: Effects of pulsed extremely-low-frequency magnetic fields on skin wounds in the rat. Bioelectromagnetics. 9:53–62. 1988. View Article : Google Scholar : PubMed/NCBI
22	Jorgensen WA, Frome BM and Wallach C: Electrochemical therapy of pelvic pain: Effects of pulsed electromagnetic fields (PEMF) on tissue trauma. Eur J Surg Suppl. 83–86. 1994.PubMed/NCBI
23	Kavand H, Haghighipour N, Zeynali B, Seyedjafari E and Abdemami B: Extremely low frequency electromagnetic field in mesenchymal stem cells gene regulation: Chondrogenic markers evaluation. Artif Organs. 40:929–937. 2016. View Article : Google Scholar : PubMed/NCBI
24	Feng SQ, Zhou XF, Rush RA and Ferguson IA: Graft of pre-injured sural nerve promotes regeneration of corticospinal tract and functional recovery in rats with chronic spinal cord injury. Brain Res 1209. 40–48. 2008. View Article : Google Scholar
25	Feng SQ, Kong XH, Guo SF, Wang P, Li L, Zhong JH and Zhou XF: Treatment of spinal cord injury with co-grafts of genetically modified Schwann cells and fetal spinal cord cell suspension in the rat. Neurotox Res. 7:169–177. 2005. View Article : Google Scholar : PubMed/NCBI
26	Kjell J and Olson L: Rat models of spinal cord injury: From pathology to potential therapies. Dis Model Mech. 9:1125–1137. 2016. View Article : Google Scholar : PubMed/NCBI
27	Cavalli G and Dinarello CA: Suppression of inflammation and acquired immunity by IL-37. Immunol Rev. 281:179–190. 2018. View Article : Google Scholar : PubMed/NCBI
28	Ni H, Jin W, Zhu T, Wang J, Yuan B, Jiang J, Liang W and Ma Z: Curcumin modulates TLR4/NF-κB inflammatory signaling pathway following traumatic spinal cord injury in rats. J Spinal Cord Med. 38:199–206. 2015. View Article : Google Scholar : PubMed/NCBI
29	Varani K, De Mattei M, Vincenzi F, Gessi S, Merighi S, Pellati A, Ongaro A, Caruso A, Cadossi R and Borea PA: Characterization of adenosine receptors in bovine chondrocytes and fibroblast-like synoviocytes exposed to low frequency low energy pulsed electromagnetic fields. Osteoarthritis Cartilage. 16:292–304. 2008. View Article : Google Scholar : PubMed/NCBI
30	Vincenzi F, Targa M, Corciulo C, Gessi S, Merighi S, Setti S, Cadossi R, Goldring MB, Borea PA and Varani K: Pulsed electromagnetic fields increased the anti-inflammatory effect of A₂A and A₃ adenosine receptors in human T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts. PLoS One. 8:e655612013. View Article : Google Scholar : PubMed/NCBI
31	Ongaro A, Varani K, Masieri FF, Pellati A, Massari L, Cadossi R, Vincenzi F, Borea PA, Fini M, Caruso A and De Mattei M: Electromagnetic fields (EMFs) and adenosine receptors modulate prostaglandin E(2) and cytokine release in human osteoarthritic synovial fibroblasts. J Cell Physiol. 227:2461–2469. 2012. View Article : Google Scholar : PubMed/NCBI
32	Visavadiya NP, Patel SP, VanRooyen JL, Sullivan PG and Rabchevsky AG: Cellular and subcellular oxidative stress parameters following severe spinal cord injury. Redox Biol. 8:59–67. 2016. View Article : Google Scholar : PubMed/NCBI
33	Yang Y, Bazhin AV, Werner J and Karakhanova S: Reactive oxygen species in the immune system. Int Rev Immunol. 32:249–270. 2013. View Article : Google Scholar : PubMed/NCBI
34	Sheng W, Zong Y, Mohammad A, Ajit D, Cui J, Han D, Hamilton JL, Simonyi A, Sun AY, Gu Z, et al: Pro-inflammatory cytokines and lipopolysaccharide induce changes in cell morphology, and upregulation of ERK1/2, iNOS and sPLA₂-IIA expression in astrocytes and microglia. J Neuroinflammation. 8:1212011. View Article : Google Scholar : PubMed/NCBI
35	Wang Q, Chen Q, Ding Q, Yang Q, Peng Y, Lu Y, Deng J and Xiong L: Sevoflurane postconditioning attenuates spinal cord reperfusion injury through free radicals-mediated up-regulation of antioxidant enzymes in rabbits. J Surg Res. 169:292–300. 2011. View Article : Google Scholar : PubMed/NCBI
36	Vincenzi F, Ravani A, Pasquini S, Merighi S, Gessi S, Setti S, Cadossi R, Borea PA and Varani K: Pulsed electromagnetic field exposure reduces Hypoxia and inflammation damage in neuron-like and microglial cells. J Cell Physiol. 232:1200–1208. 2017. View Article : Google Scholar : PubMed/NCBI
37	Jacquier-Sarlin MR, Fuller K, Dinh-Xuan AT, Richard MJ and Polla BS: Protective effects of hsp70 in inflammation. Experientia. 50:1031–1038. 1994. View Article : Google Scholar : PubMed/NCBI
38	Sevin M, Girodon F, Garrido C and de Thonel A: HSP90 and HSP70: Implication in inflammation processes and therapeutic approaches for myeloproliferative neoplasms. Mediators Inflamm 2015. 9702422015.
39	Shabbir A, Bianchetti E, Cargonja R, Petrovic A, Mladinic M, Pilipović K and Nistri A: Role of HSP70 in motoneuron survival after excitotoxic stress in a rat spinal cord injury model in vitro. Eur J Neurosci. 42:3054–3065. 2015. View Article : Google Scholar : PubMed/NCBI