Abstract
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.
Highlights
Experimental autoimmune encephalomyelitis (EAE) is an animal model of relapsing-remitting multiple sclerosis (MS)
Non-theta burst stimulation (TBS) treated groups refer to EAE and sham i/continuous TBS (cTBS) treated EAE
Thiol compounds, including GSH) and relevant antioxidant enzymes, such as superoxide dismutase (SOD) and thioredoxin reductase (TrxR) in rats immunized for EAE and during Intermittent theta burst stimulation (iTBS) and cTBS
Summary
Experimental autoimmune encephalomyelitis (EAE) is an animal model of relapsing-remitting multiple sclerosis (MS). Repeated neuroinflammatory attacks induce demyelination, neuronal damage/loss, reactive gliosis, the formation of sclerotic plaques, and aggravate remyelination. Those processes are oxidative-nitrosative stress (ONS) associated [1]. The mitochondrial respiratory chain is a primary source of reactive oxygen species (ROS). The overproduction of ROS and reactive nitrogen species (RNS). Mainly arise from activated glial and T cells and overwhelms the antioxidant capacity in EAE neuroinflammation. The central antioxidant enzymes that catalyze ROS sequestration are superoxide dismutase (SOD) and catalase. Glutathione reductase (GR), glutathione peroxidase, and glutathione-S-transferase are crucial enzymes of the glutathione cycle. Thioredoxin (Trx) and thioredoxin reductase (TrxR) make up the thioredoxin system [3].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
