Neuroprotective and antioxidant effects of docosahexaenoic acid (DHA) in an experimental model of multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating disease, whose etiology is not yet fully understood, although there are several factors that can increase the chances of suffering from it. These factors include nutrition, which may be involved in the pathogenesis of the disease. In relation to nutrition, docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (n-3 PUFA), has emerged as an important player in the regulation of neuroinflammation, being considered a pleiotropic molecule. This study aimed to evaluate the effect of DHA supplementation on clinical state and oxidative stress produced by experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Twenty-five Dark Agouti rats which were used divided into Control Group, Control+Vehicle Group, Control+DHA Group, EAE Group, and EAE+DHA Group. DHA was administered for 51 days by intraperitoneal (i.p.) injection at a dose of 40 mg/kg, once a day, 5 days a week. DHA supplementation produced a decrease in oxidative stress, as well as an improvement in the clinical score of the disease. DHA could exert a beneficial effect on the clinic of MS, through the activation of the antioxidant factor Nrf2.

Sodium chloride-induced changes in oxidative stress, inflammation, and dysbiosis in experimental multiple sclerosis.

Objectives: The high-salt diet (HSD) has been associated with cognitive dysfunction by attacking the cerebral microvasculature, through an adaptive response, initiated in the intestine and mediated by Th17 cells. In the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), it has been described that NaCl causes an increase in T cell infiltration in the central nervous system. NaCl also promotes macrophage response and Th17 cell differentiation, worsening the course of the disease. HSD may trigger an activation of the immune system and enhance inflammation. However, certain studies not only do not support this possibility, but support the opposite, as the effect of salt on immune cells may not necessarily be pathogenic. Therefore, this study aimed to evaluate the effect of an over intake of salt in rats with EAE, based on the clinical course, oxidative stress, markers of inflammation and the gut dysbiosis.Methods: 15 Dark Agouti rats were used, which were divided into control group, EAE group and EAE + NaCl group. Daily 0.027 g of NaCl dissolved in 300 µl of H2O was administered through a nasogastric tube for 51 days.Results: NaCl administration produced an improvement in clinical status and a decrease in biomarkers of oxidative stress, inflammation, and dysbiosis.Conclusion: The underlying mechanism by which NaCl causes these effects could involve the renin-angiotensin-aldosterone system (RAAS), which is blocked by high doses of salt.

Effect of the Combination of Different Therapies on Oxidative Stress in the Experimental Model of Multiple Sclerosis.

Oxidative stress is heavily involved in several pathological features of Multiple Sclerosis (MS), such as myelin destruction, axonal degeneration, and inflammation. Different therapies have been shown to reduce the oxidative stress that occurs in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Some of these therapies are transcranial magnetic stimulation (TMS), extra virgin olive oil (EVOO) and S-allyl cysteine (SAC). This study aims to test the antioxidant effect of these three therapies, to compare the efficacy of SAC versus TMS and EVOO, and to analyze the effect of combining SAC + TMS and SAC and EVOO. Seventy Dark Agouti rats were used, which were divided into Control group; Vehicle group; Mock group; SAC; EVOO; TMS; SAC + EVOO; SAC + TMS; EAE; EAE + SAC; EAE + EVOO; EAE + TMS; EAE + SAC + EVOO; EAE + SAC + TMS. The TMS consisted of an oscillatory magnetic field in the form of a sine wave with a frequency of 60 Hz and an amplitude of 0.7mT (EL-EMF) applied for two hours in the morning, once a day, five days a week. SAC was administered at a dose of 50 mg/kg body weight, orally daily, five days a week. EVOO represented 10% of their calorie intake in the total standard daily diet of rats AIN-93G. All treatments were maintained for 51 days. TMS, EVOO and SAC, alone or in combination, reduce oxidative stress, increasing antioxidant defenses and also lowering the clinical score. Combination therapies do not appear to be more potent than individual therapies against the oxidative stress of EAE or its clinical symptoms.

SARS-CoV-2 infection in multiple sclerosis patients: interaction with treatments, adjuvant therapies, and vaccines against COVID-19.

The SARS-CoV-2 pandemic has raised particular concern for people with Multiple Sclerosis, as these people are believed to be at increased risk of infection, especially those being treated with disease-modifying therapies. Therefore, the objective of this review was to describe how COVID-19 affects people who suffer from Multiple Sclerosis, evaluating the risk they have of suffering an infection by this virus, according to the therapy to which they are subjected as well as the immune response of these patients both to infection and vaccines and the neurological consequences that the virus can have in the long term. The results regarding the increased risk of infection due to treatment are contradictory. B-cell depletion therapies may cause patients to have a lower probability of generating a detectable neutralizing antibody titer. However, more studies are needed to help understand how this virus works, paying special attention to long COVID and the neurological symptoms that it causes.

Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action.

BACKGROUND: Melatonin is an indole hormone secreted primarily by the pineal gland that showing anti-oxidant, anti-inflammatory and anti-apoptotic capacity. It can play an important role in the pathophysiological mechanisms of various diseases. In this regard, different studies have shown that there is a relationship between Melatonin and Multiple Sclerosis (MS). MS is a chronic immune-mediated disease of the Central Nervous System. AIM: The objective of this review was to evaluate the mechanisms of action of melatonin on oxidative stress, inflammation and intestinal dysbiosis caused by MS, as well as its interaction with different hormones and factors that can influence the pathophysiology of the disease. RESULTS: Melatonin causes a significant increase in the levels of catalase, superoxide dismutase, glutathione peroxidase, glutathione and can counteract and inhibit the effects of the NLRP3 inflammasome, which would also be beneficial during SARS-CoV-2 infection. In addition, melatonin increases antimicrobial peptides, especially Reg3ß, which could be useful in controlling the microbiota. CONCLUSION: Melatonin could exert a beneficial effect in people suffering from MS, running as a promising candidate for the treatment of this disease. However, more research in human is needed to help understand the possible interaction between melatonin and certain sex hormones, such as estrogens, to know the potential therapeutic efficacy in both men and women.

Impact of Repetitive Transcranial Magnetic Stimulation on Neurocognition and Oxidative Stress in Relapsing-Remitting Multiple Sclerosis: A Case Report.

Multiple sclerosis (MS) is a neurodegenerative condition whose manifestation and clinical evolution can present themselves in very different ways. Analogously, its treatment has to be personalized and the patient's response may be idiosyncratic. At this moment there is no cure for it, in addition to its clinical course sometimes being torpid, with a poor response to any treatment. However, Transcranial Magnetic Stimulation (TMS) has demonstrated its usefulness as a non-invasive therapeutic tool for the treatment of some psychiatric and neurodegenerative diseases. Some studies show that the application of rTMS implies improvement in patients with MS at various levels, but the effects at the psychometric level and the redox profile in blood have never been studied before, despite the fact that both aspects have been related to the severity of MS and its evolution. Here we present the case of a woman diagnosed with relapsing-remitting multiple sclerosis (RRMS) at the age of 33, with a rapid progression of her illness and a poor response to different treatments previously prescribed for 9 years. In view of the patient's clinical course, a compassionate treatment with rTMS for 1 year was proposed. Starting from the fourth month of treatment, when reviewing the status of her disease, the patient denoted a clear improvement at different levels. There followed out psychometric evaluations and blood analyses, that showed both an improvement in her neuropsychological functions and a reduction in oxidative stress in plasma, in correspondence with therTMS treatment.

Interrelationships Among Gut Microbiota and Host: Paradigms, Role in Neurodegenerative Diseases and Future Prospects.

BACKGROUND & OBJECTIVE: Advances in the knowledge of the microbiota and concepts related to it have triggered a wake-up call in biomedicine. The development in various scientific areas has enabled a better and broader approach to everything concerning the set of families of microorganisms that coexist with an individual and are able to function as one or more organs in its body. Among the aforementioned scientific areas, those worth mentioning are the advances/progress in biotechnological resources and, in particular, molecular biology and related areas. This has given rise to the era of "omics", marking a turning point in the understanding of numerous physiologic and pathophysiologic processes of the organism. The current theory is that the microbiota and the host maintain an intimate relationship that is of a markedly bilateral nature. This continuous feedback has different connotations between one individual and another, but also within the same individual throughout its life span, which is determined by its own conditioning factors (such as its genetic profile), and environmental ones (mainly diet and lifestyles). Both elements (microbiota and host) coexist harmoniously, maintaining a balance, which can be altered and give rise to different morbid entities. Among these is its relation to chronic processes, and especially those of an autoimmune origin. Such may be neurological diseases situations and, specifically, those of a neurodegenerative nature. In disorders such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington's chorea and Alzheimer's disease, among others, it has been found that a disharmonic coexistence between microbiota and host may have implications in their etiology and pathogenesis. A better understanding of those implications has led to the development of actions on the gut microbiota as a target to slow down the advancement or establishment of neurodegeneration. CONCLUSION: In this scenario, several treatment strategies have emerged, such as probiotic food intake and stool transplantation. Their real potentialities remain to be elucidated, although current scientific evidence infers that the development of those therapeutic approaches could offer a ray of hope in the prospects of tackling neurodegenerative diseases.