Extremely Low-Frequency Electromagnetic Stimulation (ELF-EMS) Improves Neurological Outcome and Reduces Microglial Reactivity in a Rodent Model of Global Transient Stroke
Abstract
1. Introduction
2. Results
2.1. ELF-EMS Improves Outcome after Transient Global Cerebral Ischemia in Gerbils
2.2. ELF-EMS Affects Neurons and Glia in Transient Global Cerebral Ischemia
2.3. ELF-EMS Does Not Affect Neuronal Survival In Vitro but in OHSC
2.4. ELF-EMS Does Not Affect Microglia Proliferation
2.5. ELF-EMS Decreases Microglia Migration
2.5.1. LPS- and ATP-Induced Migration in BV2 Cells
2.5.2. ELF-EMS Decreases ATP Induced Migration in Primary Microglia
2.6. ELF-EMS Decreases Microglia Reactivity in Organotypic Hippocampal Slices Culture
2.7. ELF-EMS Affects Inflammation Markers in OHSC but Not in Cell Cultures
3. Discussion
4. Materials and Methods
4.1. Sinusoidal ELF-EMS
4.2. Animals
4.3. Ischemia/Reperfusion Model
4.4. Neurological and Behavior Examination
4.5. Immunofluorescence Staining of Brain Samples
4.6. Cell Culture
4.7. Organotypic Hippocampal Slice Cultures
4.8. In Vitro ‘Oxygen Glucose Deprivation/Reperfusion’ (OGD/R) Experiments
4.9. Nitrite Measurement
4.10. RNA Extraction and PCR Analysis
4.11. Migration Experiments
4.11.1. Scratch Assay
4.11.2. Transwell Migration Assay
4.12. Measurement of PI and Immunostaining of OHSC
4.13. Microglia Reactivity in OHSC
4.14. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Feigin, V.L.; Stark, B.A.; Johnson, C.O.; Roth, G.A.; Bisignano, C.; Abady, G.G.; Abbasifard, M.; Abbasi-Kangevari, M.; Abd-Allah, F.; Abedi, V.; et al. Global, Regional, and National Burden of Stroke and Its Risk Factors, 1990–2019: A Systematic Analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021, 20, 795–820. [Google Scholar] [CrossRef]
- Mosconi, M.G.; Paciaroni, M. Treatments in Ischemic Stroke: Current and Future. Eur. Neurol. 2022, 85, 349–366. [Google Scholar] [CrossRef] [PubMed]
- Lattanzi, S.; Norata, D.; Divani, A.A.; di Napoli, M.; Broggi, S.; Rocchi, C.; Ortega-Gutierrez, S.; Mansueto, G.; Silvestrini, M. Systemic Inflammatory Response Index and Futile Recanalization in Patients with Ischemic Stroke Undergoing Endovascular Treatment. Brain Sci. 2021, 11, 1164. [Google Scholar] [CrossRef] [PubMed]
- Soares, R.O.S.; Losada, D.M.; Jordani, M.C.; Évora, P.; Castro-e-Silva, O. Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies. Int. J. Mol. Sci. 2019, 20, 5034. [Google Scholar] [CrossRef] [PubMed]
- Leech, T.; Chattipakorn, N.; Chattipakorn, S.C. The Beneficial Roles of Metformin on the Brain with Cerebral Ischaemia/Reperfusion Injury. Pharmacol. Res. 2019, 146, 104261. [Google Scholar] [CrossRef]
- Dong, R.; Huang, R.; Wang, J.; Liu, H.; Xu, Z. Effects of Microglial Activation and Polarization on Brain Injury after Stroke. Front. Neurol. 2021, 12, 849. [Google Scholar] [CrossRef]
- Nour, M.; Scalzo, F.; Liebeskind, D.S. Ischemia-Reperfusion Injury in Stroke. Interv. Neurol. 2012, 1, 185–199. [Google Scholar] [CrossRef]
- Moya Gómez, A.; Font, L.P.; Brône, B.; Bronckaers, A. Electromagnetic Field as a Treatment for Cerebral Ischemic Stroke. Front. Mol. Biosci. 2021, 8, 742596. [Google Scholar] [CrossRef]
- Akdag, M.Z.; Bilgin, M.H.; Dasdag, S.; Tumer, C. Alteration of Nitric Oxide Production in Rats Exposed to a Prolonged, Extremely Low-Frequency Magnetic Field. Electromagn. Biol. Med. 2007, 26, 99–106. [Google Scholar] [CrossRef]
- Cichoń, N.; Bijak, M.; Miller, E.; Saluk, J. Extremely Low Frequency Electromagnetic Field (ELF-EMF) Reduces Oxidative Stress and Improves Functional and Psychological Status in Ischemic Stroke Patients. Bioelectromagnetics 2017, 38, 386–396. [Google Scholar] [CrossRef]
- Sakamoto, N.; Ohashi, T.; Sato, M. Effect of Magnetic Field on Nitric Oxide Synthesis of Cultured Endothelial Cells. Int. J. Appl. Electromagn. Mech. 2002, 14, 317–322. [Google Scholar] [CrossRef]
- Rappaport, Z.H.; Young, W. Effect of Pulsed Electromagnetic Fields on Calcium Tissue Changes in Focal Ischemia. Neurol. Res. 1990, 12, 95–98. [Google Scholar] [CrossRef] [PubMed]
- Kemps, H.; Dessy, C.; Dumas, L.; Sonveaux, P.; Alders, L.; Van Broeckhoven, J.; Font, L.P.; Lambrichts, S.; Foulquier, S.; Hendrix, S.; et al. Extremely Low Frequency Electromagnetic Stimulation Reduces Ischemic Stroke Volume by Improving Cerebral Collateral Blood Flow. J. Cereb. Blood Flow Metab. 2022, 42, 979–996. [Google Scholar] [CrossRef] [PubMed]
- Font, L.P.; Cardonne, M.M.; Kemps, H.; Meesen, R.; Salmon, O.F.; González, F.G.; Lambrichts, I.; Rigo, J.-M.; Brône, B.; Bronckaers, A. Non-Pulsed Sinusoidal Electromagnetic Field Rescues Animals From Severe Ischemic Stroke via NO Activation. Front. Neurosci. 2019, 13, 561. [Google Scholar] [CrossRef]
- Segal, Y.; Segal, L.; Blumenfeld-Katzir, T.; Sasson, E.; Poliansky, V.; Loeb, E.; Levy, A.; Alter, A.; Bregman, N. The Effect of Electromagnetic Field Treatment on Recovery from Ischemic Stroke in a Rat Stroke Model: Clinical, Imaging, and Pathological Findings. Stroke Res. Treat. 2016, 2016, 1–11. [Google Scholar] [CrossRef][Green Version]
- Rauš, S.; Selaković, V.; Radenović, L.; Prolić, Z.; Janać, B. Extremely Low Frequency Magnetic Field Induced Changes in Motor Behaviour of Gerbils Submitted to Global Cerebral Ischemia. Behav. Brain Res. 2012, 228, 241–246. [Google Scholar] [CrossRef]
- Rauš Balind, S.; Selaković, V.; Radenović, L.; Prolić, Z.; Janać, B. Extremely Low Frequency Magnetic Field (50 Hz, 0.5 MT) Reduces Oxidative Stress in the Brain of Gerbils Submitted to Global Cerebral Ischemia. PLoS ONE 2014, 9, e88921. [Google Scholar] [CrossRef]
- Rauš, S.; Selaković, V.; Manojlović-Stojanoski, M.; Radenović, L.; Prolić, Z.; Janać, B. Response of Hippocampal Neurons and Glial Cells to Alternating Magnetic Field in Gerbils Submitted to Global Cerebral Ischemia. Neurotox. Res. 2013, 23, 79–91. [Google Scholar] [CrossRef]
- Rawlinson, C.; Jenkins, S.; Thei, L.; Dallas, M.L.; Chen, R. Post-Ischaemic Immunological Response in the Brain: Targeting Microglia in Ischaemic Stroke Therapy. Brain Sci. 2020, 10, 159. [Google Scholar] [CrossRef]
- Nam, H.Y.; Nam, J.H.; Yoon, G.; Lee, J.-Y.; Nam, Y.; Kang, H.-J.; Cho, H.-J.; Kim, J.; Hoe, H.-S. Ibrutinib Suppresses LPS-Induced Neuroinflammatory Responses in BV2 Microglial Cells and Wild-Type Mice. J. Neuroinflamm. 2018, 15, 271. [Google Scholar] [CrossRef]
- Zhong, X.; Liu, M.; Yao, W.; Du, K.; He, M.; Jin, X.; Jiao, L.; Ma, G.; Wei, B.; Wei, M. Epigallocatechin-3-Gallate Attenuates Microglial Inflammation and Neurotoxicity by Suppressing the Activation of Canonical and Noncanonical Inflammasome via TLR4/NF-κB Pathway. Mol. Nutr. Food Res. 2019, 63, 1801230. [Google Scholar] [CrossRef] [PubMed]
- Lively, S.; Schlichter, L.C. Microglia Responses to Pro-Inflammatory Stimuli (LPS, IFNγ + TNFα) and Reprogramming by Resolving Cytokines (IL-4, IL-10). Front. Cell. Neurosci. 2018, 12, 215. [Google Scholar] [CrossRef] [PubMed]
- Wu, L.; Xiong, X.; Wu, X.; Ye, Y.; Jian, Z.; Zhi, Z.; Gu, L. Targeting Oxidative Stress and Inflammation to Prevent Ischemia-Reperfusion Injury. Front. Mol. Neurosci. 2020, 13, 28. [Google Scholar] [CrossRef] [PubMed]
- Zhang, H.; Li, L.; Sun, Y.; Zhang, X.; Zhang, Y.; Xu, S.; Zhao, P.; Liu, T. Sevoflurane Prevents Stroke-Induced Depressive and Anxiety Behaviors by Promoting Cannabinoid Receptor Subtype I-Dependent Interaction between β-Arrestin 2 and Extracellular Signal-Regulated Kinases 1/2 in the Rat Hippocampus. J. Neurochem. 2016, 137, 618–629. [Google Scholar] [CrossRef] [PubMed]
- Hillman, K.L.; Wall, H.J.; Matthews, L.O.; Gowing, E.K.; Clarkson, A.N. Altered Hippocampal–Prefrontal Dynamics Following Medial Prefrontal Stroke in Mouse. Neuromolecular. Med. 2019, 21, 401–413. [Google Scholar] [CrossRef] [PubMed]
- Guan, X.; Li, Z.; Zhu, S.; Cheng, M.; Ju, Y.; Ren, L.; Yang, G.; Min, D. Galangin Attenuated Cerebral Ischemia-Reperfusion Injury by Inhibition of Ferroptosis through Activating the SLC7A11/GPX4 Axis in Gerbils. Life Sci. 2021, 264, 118660. [Google Scholar] [CrossRef]
- Hwang, I.K.; Park, J.H.; Lee, T.-K.; Kim, D.W.; Yoo, K.-Y.; Ahn, J.H.; Kim, Y.H.; Cho, J.H.; Kim, Y.-M.; Won, M.-H.; et al. CD74-Immunoreactive Activated M1 Microglia Are Shown Late in the Gerbil Hippocampal CA1 Region Following Transient Cerebral Ischemia. Mol. Med. Rep. 2017, 15, 4148–4154. [Google Scholar] [CrossRef]
- Park, J.H.; Park, J.-A.; Ahn, J.H.; Kim, Y.H.; Kang, I.J.; Won, M.-H.; Lee, C.-H. Transient Cerebral Ischemia Induces Albumin Expression in Microglia Only in the CA1 Region of the Gerbil Hippocampus. Mol. Med. Rep. 2017, 16, 661–665. [Google Scholar] [CrossRef]
- Ahn, J.H.; Shin, M.C.; Park, J.H.; Kim, I.H.; Cho, J.-H.; Lee, T.-K.; Lee, J.-C.; Chen, B.H.; Shin, B.N.; Tae, H.-J.; et al. Effects of Long-Term Post-Ischemic Treadmill Exercise on Gliosis in the Aged Gerbil Hippocampus Induced by Transient Cerebral Ischemia. Mol. Med. Rep. 2017, 15, 3623–3630. [Google Scholar] [CrossRef]
- Jeong, D.Y.; Jeong, S.-Y.; Zhang, T.; Wu, X.; Qiu, J.Y.; Park, S. Chungkookjang, a Soy Food, Fermented with Bacillus Amyloliquefaciens Protects Gerbils against Ischemic Stroke Injury, and Post-Stroke Hyperglycemia. Food Res. Int. 2020, 128, 108769. [Google Scholar] [CrossRef]
- Park, C.W.; Lee, T.-K.; Cho, J.H.; Kim, I.H.; Lee, J.-C.; Shin, B.-N.; Ahn, J.H.; Kim, S.K.; Shin, M.C.; Ohk, T.G.; et al. Rufinamide Pretreatment Attenuates Ischemia-Reperfusion Injury in the Gerbil Hippocampus. Neurol. Res. 2017, 39, 941–952. [Google Scholar] [CrossRef] [PubMed]
- Ahn, J.H.; Shin, B.N.; Park, J.H.; Lee, T.-K.; Park, Y.E.; Lee, J.-C.; Yang, G.E.; Shin, M.C.; Cho, J.H.; Lee, K.C.; et al. Pre- and Post-Treatment with Novel Antiepileptic Drug Oxcarbazepine Exerts Neuroprotective Effect in the Hippocampus in a Gerbil Model of Transient Global Cerebral Ischemia. Brain Sci. 2019, 9, 279. [Google Scholar] [CrossRef]
- Lee, T.-K.; Ahn, J.H.; Park, C.W.; Kim, B.; Park, Y.E.; Lee, J.-C.; Park, J.H.; Yang, G.E.; Shin, M.C.; Cho, J.H.; et al. Pre-Treatment with Laminarin Protects Hippocampal CA1 Pyramidal Neurons and Attenuates Reactive Gliosis Following Transient Forebrain Ischemia in Gerbils. Mar. Drugs 2020, 18, 52. [Google Scholar] [CrossRef] [PubMed]
- Surinkaew, P.; Sawaddiruk, P.; Apaijai, N.; Chattipakorn, N.; Chattipakorn, S.C. Role of Microglia under Cardiac and Cerebral Ischemia/Reperfusion (I/R) Injury. Metab. Brain Dis. 2018, 33, 1019–1030. [Google Scholar] [CrossRef]
- Peng, J.; Wang, P.; Ge, H.; Qu, X.; Jin, X. Effects of Cordycepin on the Microglia-Overactivation-Induced Impairments of Growth and Development of Hippocampal Cultured Neurons. PLoS ONE 2015, 10, e0125902. [Google Scholar] [CrossRef] [PubMed]
- Galvani, G.; Mottolese, N.; Gennaccaro, L.; Loi, M.; Medici, G.; Tassinari, M.; Fuchs, C.; Ciani, E.; Trazzi, S. Inhibition of Microglia Overactivation Restores Neuronal Survival in a Mouse Model of CDKL5 Deficiency Disorder. J. Neuroinflamm. 2021, 18, 155. [Google Scholar] [CrossRef] [PubMed]
- Zhang, S. Microglial Activation after Ischaemic Stroke. Stroke Vasc. Neurol. 2019, 4, 71–74. [Google Scholar] [CrossRef]
- Katayama, T.; Kobayashi, H.; Okamura, T.; Yamasaki-Katayama, Y.; Kibayashi, T.; Kimura, H.; Ohsawa, K.; Kohsaka, S.; Minami, M. Accumulating Microglia Phagocytose Injured Neurons in Hippocampal Slice Cultures: Involvement of P38 MAP Kinase. PLoS ONE 2012, 7, e40813. [Google Scholar] [CrossRef]
- Wowro, S.J.; Tong, G.; Krech, J.; Rolfs, N.; Berger, F.; Schmitt, K.R.L. Combined Cyclosporin A and Hypothermia Treatment Inhibits Activation of BV-2 Microglia but Induces an Inflammatory Response in an Ischemia/Reperfusion Hippocampal Slice Culture Model. Front. Cell. Neurosci. 2019, 13, 273. [Google Scholar] [CrossRef]
- Thanh Loan, N.T.; Xoan, L.T.; Nguyet Hang, P.T.; Tai, N. Van Contribution of Ginsenosides Rg1, Rb1 to the Neuroprotective Effect of Panax Notoginseng in Mouse Organotypic Hippocampal Slice Cultures Exposed to Oxygen and Glucose Deprivation. Minist. Sci. Technol. Vietnam 2021, 63, 64–69. [Google Scholar] [CrossRef]
- Umpierre, A.D.; Wu, L.J. How Microglia Sense and Regulate Neuronal Activity. Glia 2021, 69, 1637–1653. [Google Scholar] [CrossRef] [PubMed]
- Gomes-Leal, W. Why Microglia Kill Neurons after Neural Disorders? The Friendly Fire Hypothesis. Neural Regen. Res. 2019, 14, 1499–1502. [Google Scholar] [CrossRef] [PubMed]
- Yu, Q.; Tao, H.; Wang, X.; Li, M. Targeting Brain Microvascular Endothelial Cells: A Therapeutic Approach to Neuroprotection against Stroke. Neural Regen. Res. 2015, 10, 1882. [Google Scholar] [CrossRef] [PubMed]
- Serhan, A.; Boddeke, E.; Kooijman, R. Insulin-Like Growth Factor-1 Is Neuroprotective in Aged Rats With Ischemic Stroke. Front. Aging Neurosci. 2019, 11, 349. [Google Scholar] [CrossRef]
- Rahman, M.; Luo, H.; Sims, N.R.; Bobrovskaya, L.; Zhou, X.-F. Investigation of Mature BDNF and ProBDNF Signaling in a Rat Photothrombotic Ischemic Model. Neurochem. Res. 2018, 43, 637–649. [Google Scholar] [CrossRef]
- Fan, Y.; Xie, L.; Chung, C.Y. Signaling Pathways Controlling Microglia Chemotaxis. Mol. Cells 2017, 40, 163. [Google Scholar] [CrossRef]
- Huang, M.; Wan, Y.; Mao, L.; He, Q.-W.; Xia, Y.-P.; Li, M.; Li, Y.-N.; Jin, H.-J.; Hu, B. Inhibiting the Migration of M1 Microglia at Hyperacute Period Could Improve Outcome of TMCAO Rats. CNS Neurosci. Ther. 2017, 23, 222–232. [Google Scholar] [CrossRef]
- Gómez Morillas, A.; Besson, V.C.; Lerouet, D. Microglia and Neuroinflammation: What Place for P2RY12? Int. J. Mol. Sci. 2021, 22, 1636. [Google Scholar] [CrossRef]
- Webster, C.M.; Hokari, M.; McManus, A.; Tang, X.N.; Ma, H.; Kacimi, R.; Yenari, M.A. Microglial P2Y12 Deficiency/Inhibition Protects against Brain Ischemia. PLoS ONE 2013, 8, e70927. [Google Scholar] [CrossRef]
- Xu, M.-X.; Zhao, G.-L.; Hu, X.; Zhou, H.; Li, S.-Y.; Li, F.; Miao, Y.; Lei, B.; Wang, Z. P2X7/P2X4 Receptors Mediate Proliferation and Migration of Retinal Microglia in Experimental Glaucoma in Mice. Neurosci. Bull. 2022, 38, 901–915. [Google Scholar] [CrossRef]
- Ohsawa, K.; Irino, Y.; Nakamura, Y.; Akazawa, C.; Inoue, K.; Kohsaka, S. Involvement of P2X4 and P2Y12 Receptors in ATP-Induced Microglial Chemotaxis. Glia 2007, 55, 604–616. [Google Scholar] [CrossRef]
- Srivastava, P.; Cronin, C.G.; Scranton, V.L.; Jacobson, K.A.; Liang, B.T.; Verma, R. Neuroprotective and Neuro-Rehabilitative Effects of Acute Purinergic Receptor P2X4 (P2X4R) Blockade after Ischemic Stroke. Exp. Neurol. 2020, 329, 113308. [Google Scholar] [CrossRef]
- Zhang, Y.; Li, W.; Liu, C.; Yan, J.; Yuan, X.; Wang, W.; Wang, H.; Wu, H.; Yang, Y. Electromagnetic Field Treatment Increases Purinergic Receptor P2X7 Expression and Activates Its Downstream Akt/GSK3β/β-Catenin Axis in Mesenchymal Stem Cells under Osteogenic Induction. Stem Cell. Res. Ther. 2019, 10, 407. [Google Scholar] [CrossRef] [PubMed]
- Seegers, J.C.; Lottering, L.; Joubert, A.M.; Joubert, F.; Koorts, A.; Engelbrecht, C.A.; van Papendorp, D.H. A Pulsed DC Electric Field Affects P2-Purinergic Receptor Functions by Altering the ATP Levels in in Vitro and in Vivo Systems. Med. Hypotheses 2002, 58, 171–176. [Google Scholar] [CrossRef] [PubMed]
- Zhu, T.; Kala, S.; Guo, J.; Wu, Y.; Chen, H.; Zhu, J.; Wong, K.F.; Cheung, C.P.; Huang, X.; Zhao, X.; et al. The Mechanosensitive Ion Channel Piezo1 Modulates the Migration and Immune Response of Microglia. bioRxiv 2022, 26, 496581. [Google Scholar] [CrossRef] [PubMed]
- Zhang, T.; Chi, S.; Jiang, F.; Zhao, Q.; Xiao, B. A Protein Interaction Mechanism for Suppressing the Mechanosensitive Piezo Channels. Nat. Commun. 2017, 8, 1797. [Google Scholar] [CrossRef]
- Delle Monache, S.; Alessandro, R.; Iorio, R.; Gualtieri, G.; Colonna, R. Extremely Low Frequency Electromagnetic Fields (ELF-EMFs) Induce in Vitro Angiogenesis Process in Human Endothelial Cells. Bioelectromagnetics 2008, 29, 640–648. [Google Scholar] [CrossRef]
- Peng, L.; Fu, C.; Wang, L.; Zhang, Q.; Liang, Z.; He, C.; Wei, Q. The Effect of Pulsed Electromagnetic Fields on Angiogenesis. Bioelectromagnetics 2021, 42, 250–258. [Google Scholar] [CrossRef]
- Wang, S.; Chennupati, R.; Kaur, H.; Iring, A.; Wettschureck, N.; Offermanns, S. Endothelial Cation Channel PIEZO1 Controls Blood Pressure by Mediating Flow-Induced ATP Release. J. Clin. Investig. 2016, 126, 4527–4536. [Google Scholar] [CrossRef]
- Du, L.-L.; Shen, Z.; Li, Z.; Ye, X.; Wu, M.; Hong, L.; Zhao, Y. TRPC1 Deficiency Impairs the Endothelial Progenitor Cell Function via Inhibition of Calmodulin/ENOS Pathway. J. Cardiovasc. Transl. Res. 2018, 11, 339–345. [Google Scholar] [CrossRef]
- Beeken, J.; Mertens, M.; Stas, N.; Kessels, S.; Aerts, L.; Janssen, B.; Mussen, F.; Pinto, S.; Vennekens, R.; Rigo, J.; et al. Acute Inhibition of Transient Receptor Potential Vanilloid-type 4 Cation Channel Halts Cytoskeletal Dynamism in Microglia. Glia 2022, 70, 2157–2168. [Google Scholar] [CrossRef] [PubMed]
- Shi, M.; Du, F.; Liu, Y.; Li, L.; Cai, J.; Zhang, G.-F.; Xu, X.-F.; Lin, T.; Cheng, H.-R.; Liu, X.-D.; et al. Glial Cell-Expressed Mechanosensitive Channel TRPV4 Mediates Infrasound-Induced Neuronal Impairment. Acta Neuropathol. 2013, 126, 725–739. [Google Scholar] [CrossRef] [PubMed]
- Kanju, P.; Liedtke, W. Pleiotropic Function of TRPV4 Ion Channels in the Central Nervous System. Exp. Physiol. 2016, 101, 1472–1476. [Google Scholar] [CrossRef] [PubMed]
- Jain, S.; Baratchi, S.; Pirogova, E. Low Power Microwaves Induce Changes in Gating Function of Trpv4 Ion Channel Proteins. In Proceedings of the 2017 Progress in Electromagnetics Research Symposium—Fall (PIERS—FALL), Singapore, 19–22 November 2017; IEEE: Manhattan, NY, USA, 2017; Volume 2017, pp. 1268–1272. [Google Scholar]
- Black, B.; Granja-Vazquez, R.; Johnston, B.R.; Jones, E.; Romero-Ortega, M. Anthropogenic Radio-Frequency Electromagnetic Fields Elicit Neuropathic Pain in an Amputation Model. PLoS ONE 2016, 11, e0144268. [Google Scholar] [CrossRef] [PubMed]
- Park, J.H.; Ahn, J.H.; Lee, T.-K.; Park, C.W.; Kim, B.; Lee, J.-C.; Kim, D.W.; Shin, M.C.; Cho, J.H.; Lee, C.-H.; et al. Laminarin Pretreatment Provides Neuroprotection against Forebrain Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Neuroinflammation in Aged Gerbils. Mar. Drugs 2020, 18, 213. [Google Scholar] [CrossRef]
- Wang, W.; Wang, T.; Feng, W.-Y.; Wang, Z.-Y.; Cheng, M.-S.; Wang, Y.-J. Ecdysterone Protects Gerbil Brain from Temporal Global Cerebral Ischemia/Reperfusion Injury via Preventing Neuron Apoptosis and Deactivating Astrocytes and Microglia Cells. Neurosci. Res. 2014, 81–82, 21–29. [Google Scholar] [CrossRef]
- Menzies, S.A.; Hoff, J.T.; Betz, A.L. Middle Cerebral Artery Occlusion in Rats. Neurosurgery 1992, 31, 100–107. [Google Scholar] [CrossRef]
- van den Broek, B.; Pintelon, I.; Hamad, I.; Kessels, S.; Haidar, M.; Hellings, N.; Hendriks, J.J.A.; Kleinewietfeld, M.; Brône, B.; Timmerman, V.; et al. Microglial Derived Extracellular Vesicles Activate Autophagy and Mediate Multi-target Signaling to Maintain Cellular Homeostasis. J. Extracell. Vesicles 2020, 10, e12022. [Google Scholar] [CrossRef]
- Masuch, A.; van der Pijl, R.; Füner, L.; Wolf, Y.; Eggen, B.; Boddeke, E.; Biber, K. Microglia Replenished OHSC: A Culture System to Study in Vivo like Adult Microglia. Glia 2016, 64, 1285–1297. [Google Scholar] [CrossRef]
- Miller, A.M.; Stella, N. Microglial Cell Migration Stimulated by ATP and C5a Involve Distinct Molecular Mechanisms: Quantification of Migration by a Novel near-Infrared Method. Glia 2009, 57, 875–883. [Google Scholar] [CrossRef]
- Schindelin, J.; Arganda-Carreras, I.; Frise, E.; Kaynig, V.; Longair, M.; Pietzsch, T.; Preibisch, S.; Rueden, C.; Saalfeld, S.; Schmid, B.; et al. Fiji: An Open-Source Platform for Biological-Image Analysis. Nat. Methods 2012, 9, 676–682. [Google Scholar] [CrossRef] [PubMed]
- Garcia, J.A.; Cardona, S.M.; Cardona, A.E. Analyses of Microglia Effector Function Using CX3CR1-GFP Knock-In Mice. In Methods in Molecular Biology; Clifton, N.J., Ed.; NIH Public Access: Bethesda, MA, USA, 2013; Volume 1041, pp. 307–317. [Google Scholar]
Genes | Primers (5′-3′) | |
---|---|---|
Gapdh | Forward | ACCACAGTCCATGCCATCAC |
Reversed | TCCACCACCCTGTTGCTGTA | |
Actin b | Forward | GGCTGTATTCCCCTCCATCG |
Reversed | CAGTTGGTAACAATGCCATGT | |
iNos | Forward | CCCTTCAATGGTTGGTACATGG |
Reversed | ACATTGATCTCCGTGACAGCC | |
Il-1β | Forward | ACCCTGCAGCTGGAGAGTGT |
Reversed | TTGACTTCTATCTTGTTGAAGACAAACC | |
Tnfα | Forward | CCAGACCCTCACACTCAG |
Reversed | CACTTGGTGGTTTGCTACGAC | |
Arg-1 | Forward | GTGAAGAACCCACGGTCTGT |
Reversed | GCCAGAGATGCTTCCAACTG | |
Cd163 | Forward | GCTAGACGAAGTCATCTGCACTGGG |
Reversed | TCAGCCTCAGAGACATGAACTCGG |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Moya-Gómez, A.; Font, L.P.; Burlacu, A.; Alpizar, Y.A.; Cardonne, M.M.; Brône, B.; Bronckaers, A. Extremely Low-Frequency Electromagnetic Stimulation (ELF-EMS) Improves Neurological Outcome and Reduces Microglial Reactivity in a Rodent Model of Global Transient Stroke. Int. J. Mol. Sci. 2023, 24, 11117. https://doi.org/10.3390/ijms241311117
Moya-Gómez A, Font LP, Burlacu A, Alpizar YA, Cardonne MM, Brône B, Bronckaers A. Extremely Low-Frequency Electromagnetic Stimulation (ELF-EMS) Improves Neurological Outcome and Reduces Microglial Reactivity in a Rodent Model of Global Transient Stroke. International Journal of Molecular Sciences. 2023; 24(13):11117. https://doi.org/10.3390/ijms241311117
Chicago/Turabian StyleMoya-Gómez, Amanda, Lena Pérez Font, Andreea Burlacu, Yeranddy A. Alpizar, Miriam Marañón Cardonne, Bert Brône, and Annelies Bronckaers. 2023. "Extremely Low-Frequency Electromagnetic Stimulation (ELF-EMS) Improves Neurological Outcome and Reduces Microglial Reactivity in a Rodent Model of Global Transient Stroke" International Journal of Molecular Sciences 24, no. 13: 11117. https://doi.org/10.3390/ijms241311117
APA StyleMoya-Gómez, A., Font, L. P., Burlacu, A., Alpizar, Y. A., Cardonne, M. M., Brône, B., & Bronckaers, A. (2023). Extremely Low-Frequency Electromagnetic Stimulation (ELF-EMS) Improves Neurological Outcome and Reduces Microglial Reactivity in a Rodent Model of Global Transient Stroke. International Journal of Molecular Sciences, 24(13), 11117. https://doi.org/10.3390/ijms241311117