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.

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

2020 ◽  
Author(s):  
Ivana Stevanovic ◽  
Milica Ninkovic ◽  
Bojana Mancic ◽  
Marija Milivojevic ◽  
Ivana Stojanovic ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Superoxide Anion ◽  
Thioredoxin Reductase ◽  
Female Rats ◽  
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 overproduction of reactive oxygen, nitrogen, and thiol species induced by EAE has not been entirely investigated, just as the effect of iTBS or cTBS on oxidative-nitrogen stress (ONS) in EAE rats. Dark Agouti strain female rats were tested for the effects of EAE and TBS. The rats were randomly divided into the following groups: C - control, EAE - rats immunized for EAE, CFA - rats immunized with Complete Freund's adjuvant; iTBS and cTBS groups, and EAE+iTBS and EAE+cTBS - health and EAE rats exposed to iTBS and cTBS, respectively; EAE+iTBSsh and EAE+cTBSsh - sham stimulated EAE rats with the same noise artifacts of iTBS and cTBS, respectively. 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, based on the increase of superoxide anion and lipid peroxidation; depletion of total thiols, GSH and NADPH; and decrease of SOD activity. The TrxR imposed the most sensitive response against the applied central nervous system (CNS) stressors to rats. We concluded that the TrxR upregulation meritoriously compensates decreased ROS sequestrating and GSH systems in EAE. Both iTBS and cTBS modulate the biochemical environment at a distance from the area of stimulation against ONS, accomplish a similar effect on TrxR activity to EAE and healthy rats, and alleviate symptoms of EAE.

scholarly journals Endothelial Microsomal Prostaglandin E Synthetase-1 Upregulates Vascularity and Endothelial Interleukin-1β in Deteriorative Progression of Experimental Autoimmune Encephalomyelitis

2018 ◽  
Vol 19 (11) ◽  
pp. 3647 ◽  
Author(s):  
Takako Takemiya ◽  
Marumi Kawakami ◽  
Chisen Takeuchi
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Vascular Endothelial Cells ◽  
Immunohistochemical Analysis ◽  
Interleukin 1Β ◽  
Prostaglandin E ◽  
Vascular Endothelial ◽  
Autoimmune Encephalomyelitis ◽  
Ep Receptor ◽  
Experimental Autoimmune

Microsomal prostaglandin E synthetase-1 (mPGES-1) is an inducible terminal enzyme for the production of prostaglandin E2 (PGE2). In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mPGES-1 is induced in vascular endothelial cells (VECs) around inflammatory foci and facilitates inflammation, demyelination, and paralysis. Therefore, we investigated the role of CD31-positive VECs in mPGES-1-mediated EAE aggravation using immunohistochemical analysis and imaging of wild-type (wt) and mPGES-1-deficient (mPGES-1−/−) mice. We demonstrated that EAE induction facilitated vascularity in inflammatory lesions in the spinal cord, and this was significantly higher in wt mice than in mPGES-1−/− mice. In addition, endothelial interleukin-1β (IL-1β) production was significantly higher in wt mice than in mPGES-1−/− mice. Moreover, endothelial PGE2 receptors (E-prostanoid (EP) receptors EP1–4) were expressed after EAE induction, and IL-1β was induced in EP receptor-positive VECs. Furthermore, IL-1 receptor 1 expression on VECs was increased upon EAE induction. Thus, increased vascularity is one mechanism involved in EAE aggravation induced by mPGES-1. Furthermore, mPGES-1 facilitated the autocrine function of VECs upon EP receptor induction and IL-1β production, modulating mPGES-1 induction in EAE.

scholarly journals The Immune-Modulatory Role of Apolipoprotein E with Emphasis on Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Hong-Liang Zhang ◽  
Jiang Wu ◽  
Jie Zhu
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Apolipoprotein E ◽  
T Cell Proliferation ◽  
Special Focus ◽  
Autoimmune Encephalomyelitis ◽  
Multiple Functions ◽  
Lipid Antigen ◽  
Experimental Autoimmune

Apolipoprotein E (apoE) is a 34.2 kDa glycoprotein characterized by its wide tissue distribution and multiple functions. The nonlipid-related properties of apoE include modulating inflammation and oxidation, suppressing T cell proliferation, regulating macrophage functions, and facilitating lipid antigen presentation by CD1 molecules to natural killer T (NKT) cells, and so forth. Increasing studies have revealed that APOEεallele might be associated with multiple sclerosis (MS), although evidence is still not sufficient enough. In this review, we summarized the current progress of the immunomodulatory functions of apoE, with special focus on the association of APOEεallele with the clinical features of MS and of its animal model experimental autoimmune encephalomyelitis (EAE).

Continuous versus intermittent theta burst stimulation in the treatment of experimental autoimmune encephalomyelitis: a glutamate transporters study

2020 ◽  
Author(s):  
Milica Ninkovic ◽  
Mirjana Djukic ◽  
Bojana Mancic ◽  
Petar Milosavljevic ◽  
Ivana Stojanovic ◽  
...  
Keyword(s):  
Glutamate Transporter ◽  
Glutamate Transporters ◽  
Dark Agouti ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Autoimmune Encephalomyelitis ◽  
Glial Glutamate Transporter ◽  
Elevated Expression ◽  
Underlying Mechanisms ◽  
Theta Burst

Abstract Background: Synaptic overload with glutamate aggravates neurotransmission and worsen the progression of the neurodegenerative disease, such as multiple sclerosis (MS). The experimentally induced autoimmune encephalomyelitis (EAE) in rats is a well-established animal model to study MS. Glutamate reuptake occurs by glial glutamate transporter (GLT-1), and glutamate-aspartate transporter (GLAST) localized predominantly in astrocytes terminals. The focus of the study addressing the expression of these transporters in EAE rats and those subjected to theta burst stimulation (TBS), that promotes long-lasting modulation of neuronal activity in rats/humans. Leading by the reported outcomes of TBS, we examined if TBS underlying mechanisms refer to astroglial glutamate transporters status.Methods : We studied changes in the expression of glial glutamate transporter GLT-1 and glutamate-aspartate transporter (GLAST), and glial fibrillary acidic protein (GFAP), in the spinal cord of EAE rats, subjected to intermittent (iTBS) and continuous (cTBS) theta burst stimulation. We quantified the expression of GLAST, GLT-1, and GFAP by immunofluorescence in control and experimental groups of Dark Agouti rats.Results: EAE elevated expression of GFAP, GLAST, and GLT-1. Both TBSs reduced the expression of GFAP. Continual TBS did not interfere with glutamate transporters in EAE rats, while iTBS decreased GLT-1, and increased GLAST.Conclusion: Continual TBS reduced astrogliosis more efficiently than iTBS, in EAE rats. Besides, it did not mitigate the glutamate transporters' expression; thus, glutamate reuptake remained upraised in cTBS exposed EAE rats. Accordingly, we concluded that cTBS might advance the remyelination of damaged neuronal cells in EAE rats. The future clinical trials on the treatment of MS may consider the data of this pre-clinical animal study.

scholarly journals An essential role of virus-infected B cells in the marmoset experimental autoimmune encephalomyelitis model

2017 ◽  
Vol 3 (1) ◽  
pp. 205521731769018 ◽  
Author(s):  
Bert A ’t Hart ◽  
Yolanda S Kap
Keyword(s):  
B Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Epstein Barr Virus ◽  
Infection Prevalence ◽  
Autoimmune Encephalomyelitis ◽  
Barr Virus ◽  
Experimental Autoimmune Encephalomyelitis Model ◽  
Epstein Barr ◽  
Experimental Autoimmune

Infection with Epstein–Barr virus (EBV) has been associated with an enhanced risk of genetically susceptible individuals to develop multiple sclerosis (MS). However, an explanation for the contrast between the high EBV infection prevalence (60–90%) and the low MS prevalence (0.1%) eludes us. Here we propose a new concept for the EBV–MS association developed in the experimental autoimmune encephalomyelitis model in marmoset monkeys, which are naturally infected with the EBV-related γ1-herpesvirus CalHV3. The data indicate that the infection of B cells with a γ1-herpesvirus endows them with the capacity to activate auto-aggressive CD8+ T cells specific for myelin oligodendrocyte glycoprotein.

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