Dynamic impact of brief electrical nerve stimulation on the neural immune axis—polarization of macrophages toward a pro‐repair phenotype in demyelinated peripheral nerve
Abstract
Demyelinating peripheral nerves are infiltrated by cells of the monocyte lineage, including macrophages, which are highly plastic, existing on a continuum from pro‐inflammatory M1 to pro‐repair M2 phenotypic states. Whether one can therapeutically manipulate demyelinated peripheral nerves to promote a pro‐repair M2 phenotype remains to be elucidated. We previously identified brief electrical nerve stimulation (ES) as therapeutically beneficial for remyelination, benefits which include accelerated clearance of macrophages, making us theorize that ES alters the local immune response. Thus, the impact of ES on the immune microenvironment in the zone of demyelination was examined. Adult male rat tibial nerves were focally demyelinated via 1% lysophosphatidyl choline (LPC) injection. Five days later, half underwent 1 hour 20 Hz sciatic nerve ES proximal to the LPC injection site. ES had a remarkable and significant impact, shifting the macrophage phenotype from predominantly pro‐inflammatory/M1 toward a predominantly pro‐repair/M2 one, as evidenced by an increased incidence of expression of M2‐associated phenotypic markers in identified macrophages and a decrease in M1‐associated marker expression. This was discernible at 3 days post‐ES (8 days post‐LPC) and continued at the 5 day post‐ES (10 days post‐LPC) time point examined. ES also affected chemokine (C‐C motif) ligand 2 (CCL2; aka MCP‐1) expression in a manner that correlated with increases and decreases in macrophage numbers observed in the demyelination zone. The data establish that briefly increasing neuronal activity favorably alters the immune microenvironment in demyelinated nerve, rapidly polarizing macrophages toward a pro‐repair phenotype, a beneficial therapeutic concept that may extend to other pathologies. GLIA 2016;64:1546–1561
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Local neuromodulation of damaged nerve fibers can help support peripheral nerve axonal regeneration through the activation or re-programming of myelinating Schwann cells.
“Local neuromodulation of damaged nerve fibers can help support peripheral nerve axonal regeneration through the activation or re-programming of myelinating Schwann cells [113].”
From Active Neural Interface Circuits and Systems for Selective Control of Peripheral Nerves: A Review (2024) · cites this paper as [113]
Cites
The M1 and M2 paradigm of macrophage activation: Time for reassessment
Martinez, F. O., & Gordon, S. (2014) · F1000Prime Reports · doi:10.12703/p6-13 · Cited by 4,689 · see citing works
Kigerl, K. A., Gensel, J. C., Ankeny, D. P., Alexander, J. K., Donnelly, D. J., & Popovich, P. G. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3257-09.2009 · Cited by 2,130 · see citing works
Stein, M., Keshav, S., Harris, N., & Gordon, S. (1992) · The Journal of experimental medicine · doi:10.1084/jem.176.1.287 · Cited by 1,960 · see citing works
M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
Miron, V. E., Boyd, A., Zhao, J.-W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R. J. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3469 · Cited by 1,788 · see citing works
Regulation of immune responses by L-arginine metabolism
Bronte, V., & Zanovello, P. (2005) · Nature Reviews Immunology · doi:10.1038/nri1668 · Cited by 1,775 · see citing works
Hughes, R. A., & Cornblath, D. R. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67665-9 · Cited by 1,679 · see citing works
Training induces changes in white-matter architecture
Scholz, J., Klein, M. C., Behrens, T. E. J., & Johansen-Berg, H. (2009) · Nature Neuroscience · doi:10.1038/nn.2412 · Cited by 1,508 · see citing works
Repertoire of microglial and macrophage responses after spinal cord injury
David, S., & Kroner, A. (2011) · Nature reviews. Neuroscience · doi:10.1038/nrn3053 · Cited by 1,437 · see citing works
Banati, R. B., Gehrmann, J., Schubert, P., & Kreutzberg, G. W. (1993) · Glia · doi:10.1002/glia.440070117 · Cited by 1,020 · see citing works
Stout, R. D., Jiang, C., Matta, B., Tietzel, I., Watkins, S. K., & Suttles, J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.1.342 · Cited by 968 · see citing works
Multiple Sclerosis: A Coordinated Immunological Attack against Myelin in the Central Nervous System
Steinman, L. (1996) · Cell · doi:10.1016/s0092-8674(00)81107-1 · Cited by 910 · see citing works
Brief Electrical Stimulation Promotes the Speed and Accuracy of Motor Axonal Regeneration
Al‐Majed, A. A., Neumann, C. M., Brushart, T. M. E., & Gordon, T. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-07-02602.2000 · Cited by 851 · see citing works
Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide.
Merrill, J. E., Ignarro, L. J., Sherman, M. P., Melinek, J., & Lane, T. E. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.4.2132 · Cited by 782 · see citing works
Myelin Impairs CNS Remyelination by Inhibiting Oligodendrocyte Precursor Cell Differentiation
Kotter, M. R., Li, W.-W., Zhao, C., & Franklin, R. J. M. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2615-05.2006 · Cited by 768 · see citing works
Functional plasticity of macrophages: reversible adaptation to changing microenvironments
Stout, R. D., & Suttles, J. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0504272 · Cited by 751 · see citing works
Hesse, M., Modolell, M., Flamme, A. C. L., Schito, M. L., Fuentes, J. M., Cheever, A. W., Pearce, E. J., & Wynn, T. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.11.6533 · Cited by 706 · see citing works
MicroRNA Related Polymorphisms and Breast Cancer Risk
Khan, S., Greco, D., Michailidou, K., Milne, R. L., Muranen, T., Heikkinen, T., Aaltonen, K., Dennis, J., Bolla, M. K., Liu, J., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109973 · Cited by 638 · see citing works
Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1.
Damoiseaux, J. G. M. C., Döpp, E. A., Calame, W., Chao, D., MacPherson, G. G., & Dijkstra, C. D. (1994) · PubMed Central · Cited by 515 · see citing works
Comparison of polarization properties of human adult microglia and blood‐derived macrophages
Durafourt, B. A., Moore, C. S., Zammit, D., Johnson, T., Zaguia, F., Guiot, M., Bar‐Or, A., & Antel, J. P. (2012) · Glia · doi:10.1002/glia.22298 · Cited by 470 · see citing works
Macrophages During the Fibrotic Process: M2 as Friend and Foe
Braga, T. T., Agudelo, J. S. H., & Câmara, N. O. S. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00602 · Cited by 462 · see citing works
Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression
Geremia, N. M., Gordon, T., Brushart, T. M., Al-Majed, A. A., & Verge, V. M. K. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.01.040 · Cited by 430 · see citing works
Self-citationMacrophage Diversity and Polarization in Atherosclerosis: A Question of Balance
Mantovani, A., Garlanda, C., & Locati, M. (2009) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.108.180497 · Cited by 426 · see citing works
Motor skill learning induces changes in white matter microstructure and myelination
Sampaio-Baptista, C., Khrapitchev, A. A., Foxley, S., Schlagheck, T., Scholz, J., Jbabdi, S., DeLuca, G. C., Miller, K. L., Taylor, A., Thomas, N., et al. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3048-13.2013 · Cited by 417 · see citing works
Systematic validation of specific phenotypic markers for in vitro polarized human macrophages
Ambarus, C. A., Krausz, S., van Eijk, M., Hamann, J., Radstake, T. R. D. J., Reedquist, K. A., Tak, P. P., & Baeten, D. L. P. (2012) · Journal of Immunological Methods · doi:10.1016/j.jim.2011.10.013 · Cited by 411 · see citing works
Total protein analysis as a reliable loading control for quantitative fluorescent Western blotting
Eaton, S. L., Roche, S. L., Llavero Hurtado, M., Oldknow, K. J., Farquharson, C., Gillingwater, T. H., & Wishart, T. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072457 · Cited by 403 · see citing works
Wang, G., Shi, Y., Jiang, X., Leak, R. K., Hu, X., Wu, Y., Pu, H., Li, W.-W., Tang, B., Wang, Y., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1501441112 · Cited by 376 · see citing works
Mikita, J., Dubourdieu-Cassagno, N., Deloire, M. S., Vekris, A., Biran, M., Raffard, G., Brochet, B., Canron, M.-H., Franconi, J.-M., Boiziau, C., et al. (2011) · Multiple Sclerosis Journal · doi:10.1177/1352458510379243 · Cited by 358 · see citing works
Effect of modulating macrophage phenotype on peripheral nerve repair
Mokarram, N., Merchant, A., Mukhatyar, V., Patel, G., & Bellamkonda, R. V. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.08.050 · Cited by 334 · see citing works
Macrophages in spinal cord injury: Phenotypic and functional change from exposure to myelin debris
Wang, X., Cao, K., Sun, X., Chen, Y., Duan, Z., Sun, L. J., Guo, L. M., Bai, P., Sun, D., Fan, J., et al. (2014) · Glia · doi:10.1002/glia.22774 · Cited by 319 · see citing works
Interactions between Schwann cells and macrophages in injury and inherited demyelinating disease
Martini, R., Fischer, S., López‐Vales, R., & David, S. (2008) · Glia · doi:10.1002/glia.20766 · Cited by 319 · see citing works
Gold, S. M., Schulz, K., Hartmann, S., Mladek, M., Lang, U. E., Hellweg, R., Reer, R., Braumann, K.-M., & Heesen, C. (2003) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(03)00121-8 · Cited by 300 · see citing works
Perrin, F. E. (2005) · Brain · doi:10.1093/brain/awh407 · Cited by 297 · see citing works
Endogenous BDNF is required for myelination and regeneration of injured sciatic nerve in rodents
Zhang, J. J., Luo, X., Xian, C. J., Liu, Z.-H., & Zhou, X. (2000) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2000.01312.x · Cited by 276 · see citing works
Boivin, A., Pineau, I., Barrette, B., Filali, M., Vallières, N., Rivest, S., & Lacroix, S. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3027-07.2007 · Cited by 260 · see citing works
Requirement of Myeloid Cells for Axon Regeneration
Barrette, B., Hébert, M., Filali, M., Lafortune, K., Vallières, N., Gowing, G., Julien, J., & Lacroix, S. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1447-08.2008 · Cited by 250 · see citing works
Ma, S., Chen, Y.-J., Zhang, J., Shen, L., Wang, R., Zhou, J.-S., Hu, J., & Lü, H. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.11.007 · Cited by 201 · see citing works
Macrophages and CNS remyelination
Miron, V. E., & Franklin, R. J. M. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12705 · Cited by 196 · see citing works
Kim, R. Y., Hoffman, A., Itoh, N., Ao, Y., Spence, R. D., Sofroniew, M. V., & Voskuhl, R. R. (2014) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.06.009 · Cited by 178 · see citing works
Okuda, Y., Nakatsuji, Y., Fujimura, H., Esumi, H., Ogura, T., Yanagihara, T., & Sakoda, S. (1995) · Journal of Neuroimmunology · doi:10.1016/0165-5728(95)00114-h · Cited by 176 · see citing works
Siebert, H., Sachse, A., Kuziel, W. A., Maeda, N., & Brück, W. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00343-x · Cited by 167 · see citing works
Acute injury in the peripheral nervous system triggers an alternative macrophage response
Ydens, E., Cauwels, A., Asselbergh, B., Goethals, S., Peeraer, L., Lornet, G., Almeida-Souza, L., Ginderachter, J. A. V., Timmerman, V., & Janssens, S. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-176 · Cited by 163 · see citing works
Kwon, M. J., Shin, H., Cui, Y., Kim, H., Thi, A. H. L., Choi, J.-Y., Kim, E. Y., Hwang, D., & Kim, B. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1924-15.2015 · Cited by 160 · see citing works
Acceleration in the Rate of CNS Remyelination in Lysolecithin-Induced Demyelination
Pavelko, K., van Engelen, B. V., & Rodriguez, M. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-07-02498.1998 · Cited by 140 · see citing works
Ousman, S. S., & David, S. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-13-04649.2001 · Cited by 135 · see citing works
Spontaneous and evoked activity of fetal primary afferents in vivo
Fitzgerald, M. (1987) · Nature · doi:10.1038/326603a0 · Cited by 121 · see citing works
Singh, B., Xu, Q., Franz, C. K., Zhang, R., Dalton, C., Gordon, T., Verge, V. M. K., Midha, R., & Zochodne, D. W. (2011) · Journal of neurosurgery · doi:10.3171/2011.10.jns11612 · Cited by 119 · see citing works
Self-citationRole of Macrophage Polarization in Tumor Angiogenesis and Vessel Normalization
Chen, P., & Bonaldo, P. (2013) · International review of cytology · doi:10.1016/b978-0-12-407704-1.00001-4 · Cited by 109 · see citing works
Plemel, J. R., Manesh, S. B., Sparling, J. S., & Tetzlaff, W. (2013) · Glia · doi:10.1002/glia.22535 · Cited by 107 · see citing works
Subang, M. C., & Richardson, P. M. (2001) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2001.01425.x · Cited by 91 · see citing works
Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves
ENGLISH, A. W., Liu, K., Nicolini, J., Mulligan, A., & Ye, K. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303646110 · Cited by 91 · see citing works
Macrophages express neurotrophins and neurotrophin receptors
Barouch‐Bentov, R., Appel, E., Kazimirsky, G., & Brodie, C. (2001) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00408-2 · Cited by 90 · see citing works
Tolwani, R. J., Cosgaya, J. M., Varma, S., Jacob, R., Kuo, L. E., & Shooter, E. M. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20181 · Cited by 89 · see citing works
Niemi, J. P., Oranburg, T. D., Cregg, J. M., Howarth, M., & Zigmond, R. E. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.09.018 · Cited by 86 · see citing works
Groh, J., Heinl, K., Kohl, B., Wessig, C., Greeske, J., Fischer, S., & Martini, R. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq269 · Cited by 84 · see citing works
Ji, X., Dang, Y., Gao, H., Wang, Z., Gao, M., Yang, Y., Zhang, H., & Xu, R. (2015) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-015-0182-x · Cited by 70 · see citing works
Adipose tissue insulin action and IL-6 signaling after exercise in obese mice
MACPHERSON, R. E. K., HUBER, J. S., FRENDO-CUMBO, S., SIMPSON, J. A., & WRIGHT, D. C. (2015) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000660 · Cited by 62 · see citing works
ProBDNF inhibits infiltration of ED1+ macrophages after spinal cord injury
Wong, I., Liao, H., Bai, X., Zaknic, A. V., Zhong, J., Guan, Y. H., Li, H., Wang, Y., & Zhou, X. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.01.001 · Cited by 62 · see citing works
Bernardes, D., Brambilla, R., Bracchi-Ricard, V. C., Karmally, S., Dellarole, A., Carvalho‐Tavares, J., & Bethea, J. R. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13354 · Cited by 57 · see citing works
Myers, K. J., Dougherty, J. P., & Ron, Y. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.4.2252 · Cited by 53 · see citing works
Goh, J., & Ladiges, W. (2014) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2014.06.004 · Cited by 50 · see citing works
Triarhou, L. C., & Herndon, R. (1986) · Archives of Neurology · doi:10.1001/archneur.1986.00520020015008 · Cited by 47 · see citing works
The role of chemokines in guillain–barré syndrome
Chiang, S., & Ubogu, E. E. (2013) · Muscle & Nerve · doi:10.1002/mus.23829 · Cited by 43 · see citing works
Xia, R. H., Yosef, N., & Ubogu, E. E. (2010) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2010.01092.x · Cited by 39 · see citing works
Hall, S. (1973) · Journal of Cell Science · doi:10.1242/jcs.13.2.461 · Cited by 38 · see citing works
Synthesis and release of L-serine by rat astroglia-rich primary cultures
Verleysdonk, S., & Hamprecht, B. (2000) · Glia · doi:10.1002/(sici)1098-1136(200003)30:1 · Cited by 37 · see citing works
McLean, N. A., Popescu, B. F. G., Gordon, T., Zochodne, D. W., & Verge, V. M. K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110174 · Cited by 34 · see citing works
Self-citationYuan, F., Yosef, N., Reddy, C. L., Huang, A., Chiang, S., Tithi, H. R., & Ubogu, E. E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090463 · Cited by 32 · see citing works
Mechanism of experimental autoimmune neuritis in Lewis rats: the dual role of macrophages.
Shin, T., Ahn, M., Matsumoto, Y., & Moon, C. (2013) · PubMed · doi:10.14670/hh-28.679 · Cited by 20 · see citing works
de la Hoz, C. L. R., Castro, F. R., dos Santos, L. M. B., & Langone, F. (2009) · NeuroImmunoModulation · doi:10.1159/000243086 · Cited by 14 · see citing works
Flagged first, then by citations
1 of the 70 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation
Chu, X.-L., Song, X.-Z., Li, Q., Li, Y.-R., He, F., Gu, X.-S., & Ming, D. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.335823 · Cited by 164 · see citing works
Electrospun Nanofibers for Improved Angiogenesis: Promises for Tissue Engineering Applications
Nazarnezhad, S., Baino, F., Kim, H., Webster, T. J., & Kargozar, S. (2020) · Nanomaterials · doi:10.3390/nano10081609 · Cited by 129 · see citing works
Electrical stimulation therapy for peripheral nerve injury
Ni, L., Zhao, Y. J., Zhao, Y., Zhang, T., Wang, J., Li, S., & Chen, Z. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1081458 · Cited by 109 · see citing works
Peripheral nerve injury repair by electrical stimulation combined with graphene-based scaffolds
Zhao, Y., Liu, Y., Kang, S., Sun, D., Liu, Y., Wang, X., & Lu, L. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1345163 · Cited by 85 · see citing works
Microglia: origins, homeostasis, and roles in myelin repair
Lloyd, A. F., Davies, C. L., & Miron, V. E. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.10.001 · Cited by 83 · see citing works
Javeed, S., Faraji, A. H., Dy, C. J., Ray, W. Z., & MacEwan, M. R. (2021) · Interdisciplinary Neurosurgery · doi:10.1016/j.inat.2021.101117 · Cited by 75 · see citing works
Li, X., Zhang, T., Li, C., Xu, W., Guan, Y., Li, X., Cheng, H., Chen, S., Yang, B., Liu, Y., et al. (2022) · Glia · doi:10.1002/glia.24309 · Cited by 70 · see citing works
Wang, Q., Wang, H., Ma, Y., Cao, X., & Gao, H. (2022) · Biomaterials Science · doi:10.1039/d2bm01216b · Cited by 60 · see citing works
Dong, C., Qiao, F., Hou, W., Yang, L., & Lv, Y. (2020) · Applied Materials Today · doi:10.1016/j.apmt.2020.100870 · Cited by 57 · see citing works
Electrical stimulation shifts healing/scarring towards regeneration in a rat limb amputation model
Oliveira, K. M. C., Barker, J. H., Berezikov, E., Pindur, L., Kynigopoulos, S., Eischen-Loges, M. J., Han, Z., Bhavsar, M. B., Henrich, D. M., & Leppik, L. P. (2019) · Scientific Reports · doi:10.1038/s41598-019-47389-w · Cited by 57 · see citing works
Iron Metabolism and Ferroptosis in Peripheral Nerve Injury
Huang, L., Bian, M., Zhang, J., & Jiang, L.-B. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/5918218 · Cited by 44 · see citing works
Sayanagi, J., Acevedo-Cintrón, J. A., Pan, D., Schellhardt, L., Hunter, D. A., Snyder‐Warwick, A. K., Mackinnon, S. E., & Wood, M. D. (2021) · Journal of Bone and Joint Surgery · doi:10.2106/jbjs.20.01965 · Cited by 42 · see citing works
Non-contact electrical stimulation as an effective means to promote wound healing
Xu, J., Jia, Y., Huang, W., Shi, Q., Sun, X., Zheng, L., Wang, M., Li, P., & Fan, Y. (2022) · Bioelectrochemistry · doi:10.1016/j.bioelechem.2022.108108 · Cited by 41 · see citing works
Electrical stimulation promotes the angiogenic potential of adipose-derived stem cells
Beugels, J., Molin, D. G. M., Ophelders, D. R. M. G., Rutten, T., Kessels, L. C. G. A., Kloosterboer, N., Piatkowski, A. A., Kramer, B. W. W., van der Hulst, R. R. W. J., & Wolfs, T. G. A. M. (2019) · Scientific Reports · doi:10.1038/s41598-019-48369-w · Cited by 41 · see citing works
Okayasu, T., Quesnel, A. M., O’Malley, J. T., Kamakura, T., & Nadol, J. B. (2019) · Otology & Neurotology · doi:10.1097/mao.0000000000002495 · Cited by 40 · see citing works
Zhou, M., Hu, M., He, S., Li, B., Liu, C., Min, J., & Hong, L. (2018) · Medical Science Monitor · doi:10.12659/msm.909509 · Cited by 40 · see citing works
Keane, G. C., Pan, D., Roh, J., Larson, E. L., Schellhardt, L., Hunter, D. A., Snyder‐Warwick, A. K., Moore, A. M., Mackinnon, S. E., & Wood, M. D. (2020) · Hand · doi:10.1177/1558944720939200 · Cited by 34 · see citing works
Brief Electrical Stimulation Promotes Recovery after Surgical Repair of Injured Peripheral Nerves
Gordon, T. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25010665 · Cited by 32 · see citing works
The use of electrical stimulation to enhance recovery following peripheral nerve injury
Hardy, P. B., Wang, B. Y., Chan, K. M., Webber, C. A., & Senger, J. B. (2024) · Muscle & Nerve · doi:10.1002/mus.28262 · Cited by 31 · see citing works
Thakkar, V., Mehdipour, M., & Chang, S. J. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1594435 · Cited by 31 · see citing works
Yu, B., Bai, J., Guan, Y., Huang, X., Liang, L., Ren, Z., Song, X., Zhang, T., Yang, C. H., Dai, F., et al. (2024) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2024.116578 · Cited by 27 · see citing works
Izhiman, Y., & Esfandiari, L. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1368630 · Cited by 20 · see citing works
Li, W., Zhang, G., Guan, T., Zhang, X., Khosrozadeh, A., Xing, M. M. Q., & Kong, J. (2018) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.8b00654 · Cited by 21 · see citing works
Umansky, D., Hagen, K. M., Chu, T., Pathiyil, R. K., Alzahrani, S., Ousman, S. S., & Midha, R. (2022) · Biomolecules · doi:10.3390/biom12101355 · Cited by 18 · see citing works
Park, E. Y., Lyon, J. G., Alvarado‐Velez, M., Betancur, M. I., Mokarram, N., Shin, J. H., & Bellamkonda, R. V. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24834 · Cited by 17 · see citing works
Physical modulation and peripheral nerve regeneration: a literature review
Zhai, X., & Wang, Y. (2024) · Cell Regeneration · doi:10.1186/s13619-024-00215-9 · Cited by 17 · see citing works
Ayanwuyi, L., Tokarska, N., McLean, N. A., Johnston, J., & Verge, V. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.324848 · Cited by 16 · see citing works
Self-citationZhang, L., Chen, X., Liu, Z., Han, Q., Tang, L., Tian, Z., Ren, Z., Rong, C., & Xu, H. (2019) · Brain and Behavior · doi:10.1002/brb3.1400 · Cited by 16 · see citing works
A Shock to the (Nervous) System: Bioelectricity Within Peripheral Nerve Tissue Engineering
Trueman, R. P., Ahlawat, A. S., & Phillips, J. B. (2021) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2021.0159 · Cited by 16 · see citing works
Deng, K., Balog, B. M., Lin, D., Hanzlicek, B., Song, Q., Zhu, H., & Damaser, M. S. (2019) · Interface Focus · doi:10.1098/rsfs.2019.0020 · Cited by 16 · see citing works
Yan, Y., Zhang, Y., Li, K., Li, Y., Qian, W. P., Zhang, W., Wang, Y., Ma, W., & Li, L. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.149911 · Cited by 14 · see citing works
Wu, Y., Liu, Z., Xu, Z., Zhang, Y., Ye, H., & Wang, X. (2021) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37335 · Cited by 15 · see citing works
Kawai, H. D., Ito, A., Kawaguchi, A., Nagai‐Tanima, M., Nakahara, R., Xu, S., & Kuroki, H. (2023) · Scientific Reports · doi:10.1038/s41598-023-38630-8 · Cited by 15 · see citing works
Fabrication of piezoelectric/conductive composite nerve conduits for peripheral nerve regeneration
Bian, T., Jiang, Y., Cao, J., Wu, W.-J., Zhang, L., & Yang, Y. (2025) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2025.114544 · Cited by 14 · see citing works
Tokarska, N., Naniong, J. M. A., Johnston, J. M., Salapa, H. E., Muir, G. D., Levin, M. C., Popescu, B. F. G., & Verge, V. M. K. (2023) · Glia · doi:10.1002/glia.24381 · Cited by 12 · see citing works
Self-citationConductive hydrogels as an “innovative healer” for the treatment of diabetic wounds
Zhao, J., Gao, C., Guo, W., Zhang, B., Ren, S., Wu, S., Guo, J. Q., & Qu, W. (2024) · Materials Chemistry Frontiers · doi:10.1039/d4qm00405a · Cited by 12 · see citing works
Zhang, N., Yao, X., Zhang, Q., Zhang, C., Zheng, Q., Wang, Y., & Shan, F. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2025.167804 · Cited by 12 · see citing works
Research progress in different physical therapies for treating peripheral nerve injuries
Chu, X., Zhao, X., Liu, S. J., Li, Y., Ding, N., Liu, M.-Q., Li, Q., & Li, Q. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1508604 · Cited by 13 · see citing works
Active Neural Interface Circuits and Systems for Selective Control of Peripheral Nerves: A Review
Habibollahi, M., Jiang, D., Lancashire, H. T., & Demosthenous, A. (2024) · IEEE Transactions on Biomedical Circuits and Systems · doi:10.1109/tbcas.2024.3430038 · Cited by 11 · see citing works
“Local neuromodulation of damaged nerve fibers can help support peripheral nerve axonal regeneration through the activation or re-programming of myelinating Schwann cells [113].”
Chen, Y.-S., Chang, S., Ng, H. Y., Huang, Y., Chen, C.-C., & Shie, M. (2021) · Processes · doi:10.3390/pr9020353 · Cited by 10 · see citing works
Integrated implantable triboelectric charge collector for nerve repair
Cai, C., Wang, T., Zhang, Y., Lin, C., Feng, Z., Cai, Y., & He, N. (2025) · Chinese Chemical Letters · doi:10.1016/j.cclet.2025.111087 · Cited by 7 · see citing works
Tian, T. M., Kim, D. D., Yu, K., Hartzell, H. C., & Ward, P. J. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106893 · Cited by 8 · see citing works
Warner, W. S., Stubben, C., Yeoh, S., Light, A. R., & Mahan, M. A. (2023) · Scientific Reports · doi:10.1038/s41598-023-35606-6 · Cited by 7 · see citing works
Senger, J. B., Power, H. A., & Moore, A. M. (2024) · Hand Clinics · doi:10.1016/j.hcl.2024.03.007 · Cited by 6 · see citing works
Warner, W. S., Rose, M., Yeoh, S., Muhlestein, W. E., Gilandehi, S. N., & Mahan, M. A. (2026) · Frontiers in Surgery · doi:10.3389/fsurg.2026.1745990 · Cited by 5 · see citing works
Hardy, P. B., Wang, B. Y., Chan, K. M., Webber, C. A., & Senger, J. B. (2025) · Muscle & Nerve · doi:10.1002/mus.28385 · Cited by 5 · see citing works
Coroneos, C. J., Levis, C. M., Willand, M. P., So, K. J. W., & Bain, J. R. (2025) · Bioelectronic Medicine · doi:10.1186/s42234-025-00171-y · Cited by 5 · see citing works
Hazer, D. B., Stenberg, L., Mahlapuu, M., & Dahlin, L. B. (2024) · Regenerative Medicine · doi:10.1080/17460751.2024.2361515 · Cited by 4 · see citing works
Brief Electrical Stimulation Triggers an Effective Regeneration of Leech CNS
Cohen, S., Richter-Levin, A., & Shefi, O. (2020) · eNeuro · doi:10.1523/eneuro.0030-19.2020 · Cited by 4 · see citing works
Commentary: Rapid-Stretch Injury to Peripheral Nerves: Histologic Results
Umansky, D., & Midha, R. (2019) · Neurosurgery · doi:10.1093/neuros/nyz196 · Cited by 4 · see citing works
Naseri, S., Samaram, H., Naghavi, N., Rassouli, M. B., & Mousavinezhad-Moghaddam, M. (2024) · Neurochemical Research · doi:10.1007/s11064-024-04154-4 · Cited by 3 · see citing works
Conditioning Electrical Stimulation Fails to Enhance Sympathetic Axon Regeneration
Tian, T. M., Patel, K., Kim, D., SiMa, H., Harris, A. R., Owyoung, J. N., & Ward, P. J. (2025) · Neurorehabilitation and neural repair · doi:10.1177/15459683251335321 · Cited by 3 · see citing works
Tokarska, N., Roberts, J., Koralage, S. R., Naniong, J. M., Johnston, J., Wei, Z.-L., & Verge, V. (2025) · Glia · doi:10.1002/glia.70127 · Cited by 1 · see citing works
Self-citationLi, W. (2018) · Mspace (University of Manitoba)
[Progress of electrical stimulation to promote peripheral nerve regeneration].
Chen, H., Feng, G., & Zhao, Y. (2024) · PubMed Central · doi:10.13201/j.issn.2096-7993.2024.05.012 · Cited by 1 · see citing works
Shchudlo, N. A., Варсегова, Т. Н., & Stupina, T. A. (2024) · Genij Ortopedii · doi:10.18019/1028-4427-2024-30-3-417-426
Bridging the Gap: Contemporary Paradigms in Nerve Scaffolds and Regeneration
Hwang, C. D., Caragher, S. P., Bihun, R. J., & Eberlin, K. R. (2025) · Advances in Wound Care · doi:10.1089/wound.2024.0074
Puder, J. M., Jablonka‐Shariff, A., Wood, M. D., & Snyder‐Warwick, A. K. (2025) · Muscle & Nerve · doi:10.1002/mus.70020
Noninvasive transcranial brain stimulation to treat cognitive aspects of multiple sclerosis
Schependom, J. V., Scheinok, T., Grognard, M., Nagels, G., & D'haeseleer, M. (2025) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-443-26602-7.00021-x
Ran, R., Zhao, Y., Zhao, J., Hu, L., Zhang, S., Gong, C., Guo, C., Shan, M., Wang, R., Xie, Q. M., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-9107953/v1
Guo, D., Xiao, L., Xu, K., Li, H., Li, Z., Pan, Y., & Zhang, H. (2026) · Materials Today Advances · doi:10.1016/j.mtadv.2026.100934
Self-powered functional materials for immune modulation by electrical stimulation
Peng, S., Wang, Y., Yang, R., Wang, Y., Sun, Q., Zhang, Y., & Gao, S. (2026) · Materials & Design · doi:10.1016/j.matdes.2026.117060
- Authors
- MLean, N. A., & Verge, V. M. K.
- Affiliations
- University of Saskatchewan (CA)
- Corresponding author
- Verge, Valerie M. K.
- ORCID
- Verge, Valerie M. K.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2016-06-29
- Volume
- 64
- Issue
- 9
- Pages
- 1546-1561
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2466542860
- Cited by
- 62
- References
- 70
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 14 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 1
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP74747)
- Saskatchewan Health Research Foundation (2803)
- Multiple Sclerosis Society of Canada (2362)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- electrical nerve stimulation, macrophage polarization, M2 macrophages, M1 macrophages, demyelination, peripheral nerves, remyelination, lysophosphatidylcholine, immune microenvironment, CCL2/MCP-1, neuroinflammation, sciatic nerve, glial scar
- MeSH terms
- Animals, Axons, Demyelinating Diseases, Electric Stimulation, Macrophages, Male, Monocytes, Myelin Sheath, Nerve Regeneration, Schwann Cells, Sciatic Nerve, Rats, Wistar
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