scholarly journals Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis

2021 ◽  
Vol 11 (6) ◽  
pp. 736
Author(s):  
Milorad Dragić ◽  
Milica Zeljković ◽  
Ivana Stevanović ◽  
Marija Adžić ◽  
Andjela Stekić ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Glial Cells ◽  
Magnetic Stimulation ◽  
Purinergic Signaling ◽  
Cranial Bone ◽  
Autoimmune Encephalomyelitis ◽  
Anti Inflammatory ◽  
Theta Burst ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by autoimmune-mediated inflammation in the central nervous system. Purinergic signaling is critically involved in MS-associated neuroinflammation and its most widely applied animal model—experimental autoimmune encephalomyelitis (EAE). A promising but poorly understood approach in the treatment of MS is repetitive transcranial magnetic stimulation. In the present study, we aimed to investigate the effect of continuous theta-burst stimulation (CTBS), applied over frontal cranial bone, on the adenosine-mediated signaling system in EAE, particularly on CD73/A2AR/A1R in the context of neuroinflammatory activation of glial cells. EAE was induced in two-month-old female DA rats and in the disease peak treated with CTBS protocol for ten consecutive days. Lumbosacral spinal cord was analyzed immunohistochemically for adenosine-mediated signaling components and pro- and anti-inflammatory factors. We found downregulated IL-1β and NF- κB-ir and upregulated IL-10 pointing towards a reduction in the neuroinflammatory process in EAE animals after CTBS treatment. Furthermore, CTBS attenuated EAE-induced glial eN/CD73 expression and activity, while inducing a shift in A2AR expression from glia to neurons, contrary to EAE, where tight coupling of eN/CD73 and A2AR on glial cells is observed. Finally, increased glial A1R expression following CTBS supports anti-inflammatory adenosine actions and potentially contributes to the overall neuroprotective effect observed in EAE animals after CTBS treatment.

Comparative of transcranial magnetic stimulation and other treatments in experimental autoimmune encephalomyelitis

2018 ◽  
Vol 137 ◽  
pp. 140-145 ◽  
Author(s):  
Francisco J. Medina-Fernandez ◽  
Begoña M. Escribano ◽  
Evelio Luque ◽  
Javier Caballero-Villarraso ◽  
Jose L. Gomez-Chaparro ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Magnetic Stimulation ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Effects of transcranial magnetic stimulation on oxidative stress in experimental autoimmune encephalomyelitis

2017 ◽  
Vol 51 (5) ◽  
pp. 460-469 ◽  
Author(s):  
Francisco J. Medina-Fernandez ◽  
Begoña M. Escribano ◽  
Eduardo Agüera ◽  
Macarena Aguilar-Luque ◽  
Montserrat Feijoo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcranial Magnetic Stimulation ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Magnetic Stimulation ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Transcranial magnetic stimulation modifies astrocytosis, cell density and lipopolysaccharide levels in experimental autoimmune encephalomyelitis

Life Sciences ◽  
2017 ◽  
Vol 169 ◽  
pp. 20-26 ◽  
Author(s):  
Francisco J. Medina-Fernández ◽  
Evelio Luque ◽  
Macarena Aguilar-Luque ◽  
Eduardo Agüera ◽  
Montserrat Feijóo ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Cell Density ◽  
Magnetic Stimulation ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals Transcranial Magnetic Stimulation Improves Muscle Involvement in Experimental Autoimmune Encephalomyelitis

2021 ◽  
Vol 22 (16) ◽  
pp. 8589
Author(s):  
Maria Angeles Peña-Toledo ◽  
Evelio Luque ◽  
Ignacio Ruz-Caracuel ◽  
Eduardo Agüera ◽  
Ignacio Jimena ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Skeletal Muscle ◽  
Transcranial Magnetic Stimulation ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Magnetic Stimulation ◽  
Clinical Severity ◽  
Autoimmune Encephalomyelitis ◽  
Muscle Involvement ◽  
Experimental Autoimmune

Skeletal muscle is affected in experimental autoimmune encephalomyelitis (EAE), which is a model of multiple sclerosis that produces changes including muscle atrophy; histological features of neurogenic involvement, and increased oxidative stress. In this study, we aimed to evaluate the therapeutic effects of transcranial magnetic stimulation (TMS) on the involvement of rat skeletal muscle and to compare them with those produced by natalizumab (NTZ). EAE was induced by injecting myelin oligodendrocyte glycoprotein (MOG) into Dark Agouti rats. Both treatments, NTZ and TMS, were implemented from day 15 to day 35. Clinical severity was studied, and after sacrifice, the soleus and extensor digitorum longus muscles were extracted for subsequent histological and biochemical analysis. The treatment with TMS and NTZ had a beneficial effect on muscle involvement in the EAE model. There was a clinical improvement in functional motor deficits, atrophy was attenuated, neurogenic muscle lesions were reduced, and the level of oxidative stress biomarkers was lower in both treatment groups. Compared to NTZ, the best response was obtained with TMS for all the parameters analyzed. The myoprotective effect of TMS was higher than that of NTZ. Thus, the use of TMS may be an effective strategy to reduce muscle involvement in multiple sclerosis.

scholarly journals Compensatory Neuroprotective Response of Thioredoxin Reductase against Oxidative-Nitrosative Stress Induced by Experimental Autoimmune Encephalomyelitis in Rats: Modulation by Theta Burst Stimulation

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3922
Author(s):  
Ivana Stevanovic ◽  
Milica Ninkovic ◽  
Bojana Mancic ◽  
Marija Milivojevic ◽  
Ivana Stojanovic ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Thioredoxin Reductase ◽  
Female Rats ◽  
Health Improvement ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Autoimmune Encephalomyelitis ◽  
Theta Burst ◽  
Experimental Autoimmune

Cortical theta burst stimulation (TBS) structured as intermittent (iTBS) and continuous (cTBS) could prevent the progression of the experimental autoimmune encephalomyelitis (EAE). The interplay of brain antioxidant defense systems against free radicals (FRs) overproduction induced by EAE, as well as during iTBS or cTBS, have not been entirely investigated. This study aimed to examine whether oxidative-nitrogen stress (ONS) is one of the underlying pathophysiological mechanisms of EAE, which may be changed in terms of health improvement by iTBS or cTBS. Dark Agouti strain female rats were tested for the effects of EAE and TBS. The rats were randomly divided into the control group, rats specifically immunized for EAE and nonspecifically immuno-stimulated with Complete Freund’s adjuvant. TBS or sham TBS was applied to EAE rats from 14th–24th post-immunization day. Superoxide dismutase activity, levels of superoxide anion (O2•–), lipid peroxidation, glutathione (GSH), nicotinamide adenine dinucleotide phosphate (NADPH), and thioredoxin reductase (TrxR) activity were analyzed in rat spinal cords homogenates. The severity of EAE clinical coincided with the climax of ONS. The most critical result refers to TrxR, which immensely responded against the applied stressors of the central nervous system (CNS), including immunization and TBS. We found that the compensatory neuroprotective role of TrxR upregulation is a positive feedback mechanism that reduces the harmfulness of ONS. iTBS and cTBS both modulate the biochemical environment against ONS at a distance from the area of stimulation, alleviating symptoms of EAE. The results of our study increase the understanding of FRs’ interplay and the role of Trx/TrxR in ONS-associated neuroinflammatory diseases, such as EAE. Also, our results might help the development of new ideas for designing more effective medical treatment, combining neuropsychological with noninvasive neurostimulation–neuromodulation techniques to patients living with MS.

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