Isaac Túnez

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method with neuromodulatory capacity in neurodegenerative diseases such as multiple sclerosis (MS). Its therapeutic value is linked to its activity against oxidative stress by activation of antioxidant defenses. The sex hormones, estrogens (E), progesterone (P) and testosterone (T), have demonstrated their power as adjuvants to TMS, improving cortical excitability. The aim of this study was to evaluate the effect of these hormones as adjuvants to extremely low-frequency electromagnetic fields (ELFEFs) in the treatment of experimental autoimmune encephalomyelitis (EAE), the experimental model of MS. The effect of these hormones as replacement therapy was also evaluated in ovariectomized rats treated with ELFEFs. Sixty-five female Dark Agouti rats were divided into 13 groups (5 rats/group), in which biomarkers of oxidative stress and the glutathione redox cycle in non-nervous organs (kidney, liver, heart, intestines and blood) were analyzed. The results show that ELFEFs alone are more effective against oxidative stress. However, P and E were more effective than ELFEFs, both as adjuvants and in hormone replacement therapy, in activating the glutathione system. Therefore, it could be concluded that sex hormones play an important role against MS, enhancing the antioxidant effect of ELFEFs.

Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system (CNS). By acting on the immune system, disease-modifying therapies (DMTs) can control disease activity, but they indirectly increase susceptibility to infections, so different vaccines are necessary to prevent it. DMTs may potentially affect vaccine-induced seroconversion. We aim to analyse the response to the hepatitis B virus (HBV) vaccine (Engerix-B) in relapsing–remitting MS patients (RRMS) using these therapies because the scientific literature remains limited in this area. A retrospective observational study of RRMS patients vaccinated against HBV was conducted. Acquired immunity after vaccination was determined, and an analysis of immunogenicity was conducted based on the type of DMT (immunomodulators/immunosuppressants), vaccine doses, total lymphocyte count (TLC), age, and sex. 200 patients were included, with a mean age 47.79 years, and 140 (70%) were women. A lower vaccine response was observed in patients treated with immunosuppressive DMTs (51.8%, p < 0.001), particularly with fingolimod (32.4%, p < 0.001), and a higher response was seen with immunomodulators like teriflunomide and interferon-β1a (100%, p < 0.001). Using logistic regression, a model was obtained that included the number of vaccine cycles, lymphopenia and type of DMT associated with the response to the HBV vaccine. It is necessary to adapt HBV vaccination protocols for MS patients, considering the type of DMT used and baseline immune status.

Background: Multiple sclerosis (MS) is an autoimmune neurodegenerative disease with a higher prevalence in women. While puberty appears to act as a trigger for MS, menopause has no clear effects on disease progression. Many studies have shown that transcranial magnetic stimulation (TMS) is a potential antioxidant treatment for MS, but the sexual hormones have been identified as a potential factor affecting TMS response by affecting cortical excitability and possibly clinical outcomes. Methods: The aim of this study was to test the effect of estrogen, progesterone, and testosterone hormonal supplementation as adjuvants to TMS treatment of experimental autoimmune encephalomyelitis (EAE), an experimental model of MS. The effects of the three hormones were also tested as replacement therapy in ovariectomized rats treated with TMS. Clinical signs of the disease, as well as disease-induced oxidative stress and antioxidant defenses of the glutathione system, were evaluated. Results: TMS alone, without supplements or replacement therapies, is effective against oxidative stress caused by EAE. Estrogen and progesterone replacement therapy is useful to enhance the role of TMS in ovariectomized rats, activating antioxidant defenses and improving clinical signs of the disease. Conclusions: TMS is effective in the treatment of MS, but its role could be enhanced, using hormone replacement therapy with estrogens and/or progesterone.

The bidirectional relationship between the brain and gut microbiota has led to the concept of the microbiota–gut–brain axis. It refers to a system of bilateral communication that integrates neuronal, immunological, and metabolic signals, whose disruption has been linked to the pathogenesis of digestive, metabolic, and neurological disorders, among others. Intestinal dysbiosis (an imbalance in the gut microbiota) can promote a proinflammatory and prothrombotic state, as well as dyslipidaemia and dysglycemia, that increase atherogenic risk and consequently the risk of stroke. Dysbiosis can also lead to neuroinflammatory and neurodegenerative effects, compromising the integrity of the blood–brain barrier and exacerbating brain injury after stroke. Specific bacterial profiles have been associated with varying levels of stroke risk, emphasising the role of gut microbiota-derived vasoactive metabolites such as Trimethylamine N-Oxide (TMAO), phenylacetylglnutamine (PAGln), and short-chain fatty acids (SCFAs), which may serve as biomarkers for stroke risk and severity. Gut microbiota also influences neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), involved in recovery after stroke. Research has explored the potential to modify the gut microbiota to either prevent stroke (by reducing risk) or improve outcomes (by decreasing severity and sequelae). Current scientific evidence supports the role of gut microbiota as a potential diagnostic and prognostic biomarker, as well as a therapeutic target.

Background/Objectives: Dopamine replacement therapy for Parkinson’s disease (PD) may lead to disabling incontrollable movements known as L-DOPA-induced dyskinesias. Transcranial magnetic stimulation (TMS) has been applied as non-invasive therapy to ameliorate motor symptoms and dyskinesias in PD treatment. Recent studies have shown that TMS-induced motor effects might be related to dopaminergic system modulation. However, the mechanisms underlying these effects of TMS are not fully understood. Objectives: To assess the expression of FosB and c-Fos in dopamine-D1 receptor-containing cells of dyskinetic rats and to analyze the effect of TMS on dyskinetic behavior and its histological marker (FosB). Methods: We investigated the outcome of TMS on cellular activation, using c-Fos immunoreactivity, on D1 receptor-positive (D1R+) cells into the motor cortex and striatum of dyskinetic (n = 14) and intact rats (n = 14). Additionally, we evaluated the effect of TMS on the dyskinesia global score and its molecular marker, FosB, in the striatum (n = 67). Results: TMS reduces c-Fos expression in D1R+cells into the motor cortex and striatum. Moreover, TMS treatment attenuated dyskinesias, along with a low stratal FosB expression. Conclusions: The current study shows that TMS depressed FosB and c-Fos expression in D1R+ cells of the dorsal striatum and motor cortex, in accordance with previous evidence of its capacity to modulate the dopaminergic system, thus suggesting a mechanism by which TMS may mitigate dyskinesias. Additionally, our observations highlight the potential therapeutic effect of TMS on dyskinesias in a PD model.

There is substantial evidence supporting the neuroprotective effects of the MIND diet in neurodegenerative diseases like Parkinson’s and Alzheimer’s. Our aim was to evaluate the impact of a nutritional intervention (NI) with this diet on multiple sclerosis (MS) patients. The study was conducted in two stages. In the first stage, two groups were included: MS patients before the NI (group A) and healthy control subjects (group B). In this stage, groups (A) and (B) were compared (case–control study). In the second stage, group (A) was assessed after the NI, with comparisons made between baseline and final measurements (before-and-after study). In the case–control stage (baseline evaluation), we found significant differences in fatigue scores (p < 0.001), adherence to the MIND diet (p < 0.001), the serum levels of brain-derived neurotrophic factor (BDNF) (p < 0.001), and higher oxidative status in the MS group, with lower levels of reduced glutathione (p < 0.001), reduced/oxidised glutathione ratio (p < 0.001), and elevated levels of lipoperoxidation (p < 0.002) and 8-hydroxy-2′-deoxyguanosine (p < 0.025). The before-and-after intervention stage showed improvements in fatigue scores (p < 0.001) and physical quality-of-life scores (MSQOL-54) (p < 0.022), along with decreases in the serum levels of glial-derived neurotrophic factor (GDNF) (p < 0.041), lipoperoxidation (p < 0.046), and 8-hydroxy-2′-deoxyguanosine (p < 0.05). Consumption of the MIND diet is linked to clinical and biochemical improvement in MS patients.

Multiple sclerosis (MS) is characterized by a variety of symptoms that have a major impact on quality of life (QoL) even in early stages. In addition to individual motor, sensory, visual disturbances, and brainstem and sphincter disorders, which are expressed through the widely used Expanded Disability Status Scale (EDSS), other manifestations of MS have a detrimental effect on overall functioning and quality of life, such as cognitive impairment, depression, anxiety, fatigue, and pain. However, when talking about QoL, categorical definitions cannot be used because although the concept is generally understood, it is highly nuanced. Suffering from MS can significantly reduce QoL. Numerous research studies have focused on trying to identify and assess which are the elements that most affect the loss of QoL in MS people. However, in addition to the fact that the measurement of QoL can be subjective, it is very difficult to consider these elements in isolation, as they are interrelated. One such limiting factor of QoL that has been investigated is cognitive impairment (CI). This has been shown to have an impact on the lives of MS people, although the different approaches that have been taken to assess CI have evident limitations.