The mechanism of action of methylprednisolone in the treatment of multiple sclerosis

2005 ◽  
Vol 11 (4) ◽  
pp. 425-432 ◽  
Author(s):  
J S Sloka ◽  
M Stefanelli
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Current Treatment ◽  
Necrosis Factor Alpha ◽  
Cytotoxic Effects ◽  
Treatment Regimes ◽  
The Central Nervous System ◽  
Factor Alpha ◽  
Cytokine Cascade ◽  
The Individual

Methylprednisolone plays an important role in the current treatment of multiple sclerosis (MS), particularly in the acute phase of relapse. It acts in various ways to decrease the inflammatory cycle including: dampening the inflammatory cytokine cascade, inhibiting the activation of T cells, decreasing the extravasation of immune cells into the central nervous system, facilitating the apoptosis of activated immune cells, and indirectly decreasing the cytotoxic effects of nitric oxide and tumor necrosis factor alpha. This paper reviews the most recent observations on these mechanisms both to understand the disease mechanism and its treatment. As more becomes known about these mechanisms, it may become possible to design treatment regimes that are more specific towards both the individual and the disease state.

scholarly journals Absence of cytotoxicity towards microglia of iron oxide (α-Fe2O3) nanorhombohedra

2016 ◽  
Vol 5 (3) ◽  
pp. 836-847 ◽  
Author(s):  
Crystal S. Lewis ◽  
Luisa Torres ◽  
Jeremy T. Miyauchi ◽  
Cyrus Rastegar ◽  
Jonathan M. Patete ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Necrosis Factor Alpha ◽  
Cytotoxic Effects ◽  
Nanoparticle Exposure ◽  
Cellular Iron ◽  
Therapeutic Setting ◽  
The Central Nervous System ◽  
Factor Alpha

Abstract Understanding the nature of interactions between nanomaterials, such as commercially ubiquitous hematite (α-Fe2O3) nanorhombohedra (N-Rhomb) and biological systems is of critical importance for gaining insight into the practical applicability of nanomaterials. Microglia represent the first line of defense in the central nervous system (CNS) during severe injury or disease such as Parkinson's and Alzheimer's disease as illustrative examples. Hence, to analyze the potential cytotoxic effect of N-Rhomb exposure in the presence of microglia, we have synthesized Rhodamine B (RhB)-labeled α-Fe2O3 N-Rhomb, with lengths of 47 ± 10 nm and widths of 35 ± 8 nm. Internalization of RhB-labeled α-Fe2O3 N-Rhomb by microglia in the mouse brain was observed, and a dose-dependent increase in the cellular iron content as probed by cellular fluorescence was detected in cultured microglia after nanoparticle exposure. The cells maintained clear functional viability, exhibiting little to no cytotoxic effects after 24 and 48 hours at acceptable, physiological concentrations. Importantly, the nanoparticle exposure did not induce microglial cells to produce either tumor necrosis factor alpha (TNFα) or interleukin 1-beta (IL1β), two pro-inflammatory cytokines, nor did exposure stimulate the production of nitrites and reactive oxygen species (ROS), which are common indicators for the onset of inflammation. Finally, we propose that under the conditions of our experiments, i.e. in the presence of RhB labeled-α-Fe2O3 N-Rhomb maintaining concentrations of up to 100 μg mL−1 after 48 hours of incubation, the in vitro and in vivo internalization of RhB-labeled α-Fe2O3 N-Rhomb are likely to be clathrin-dependent, which represents a conventional mechanistic uptake route for most cells. Given the crucial role that microglia play in many neurological disorders, understanding the potential cytotoxic effects of these nanostructures is of fundamental importance if they are to be used in a therapeutic setting.

Cold-induced reactivity in multiple sclerosis patients

2017 ◽  
pp. 56-62 ◽  
Author(s):  
Л.И. Герасимова-Мейгал ◽  
И.М. Сиренев
Keyword(s):  
Multiple Sclerosis ◽  
Cold Test ◽  
Typical Feature ◽  
Humid Climate ◽  
Ssr Analysis ◽  
Epidemiological Surveys ◽  
The Central Nervous System ◽  
The Individual ◽  
Hands And Feet ◽  
Multiple Sclerosis Patients

Цель исследования - изучение особенностей восприимчивости пациентов с рассеянным склерозом (РС) к холодовому воздействию с помощью функциональных тестов, характеризующих функцию терморегуляции. Как известно, РС - хроническое прогрессирующее аутоиммунное заболевание центральной нервной системы мультифакториальной природы, более часто встречающееся в регионах с холодным и влажным климатом. Нарушения терморегуляции вследствие автономной дисфункции являются характерным признаком РС, вместе с тем участию холодового фактора в развитии заболевания не придается существенного значения. Методика. Обследовано 32 пациента (17 мужчин и 15 женщин, средний возраст 29,6 ± 4,2 года) с установленным диагнозом: РС ремиттирующе-рецидивирующая форма течения (средняя продолжительность заболевания - 4,2 ± 2,7 года) и 18 практически здоровых лиц группы сравнения. Восприятие холода оценивали с помощью визуально-аналоговой шкалы. Продолжительность холод-индуцированной вазоконстрикции после локального холодового теста изучали по данным инфракрасной термометрии. Вегетативную регуляцию вазомоторных реакций оценивали по результатам анализа вызванных кожных вегетативных потенциалов (ВКВП). Результаты. На основе анализа самооценки восприятия холода у пациентов с РС показана низкая переносимость холодового фактора. При проведении локального холодового теста отмечено замедление восстановления температуры кожи кисти, что характерно для усиления холод-индуцированной вазоконстрикции. В группе пациентов с РС выявлено снижение параметров ВКВП ладоней и стоп, свидетельствующее о дефиците нейрогенного контроля терморегуляционных сосудистых реакций. Заключение. У пациентов с РС выявлены нарушения механизмов терморегуляции при действии холода, что обусловливает высокую индивидуальную восприимчивость к холоду у данной категории лиц. Сопоставление результатов анализа механизмов индивидуальной холод-индуцированной реактивности у пациентов с РС с данными эпидемиологических исследований приводит к заключению о потенциальном модулирующем влиянии холодового фактора на течение РС. The purpose of the present study was focused on the evaluation of the sensitivity to cold in multiple sclerosis (MS) patients by means of functional thermoregulatory based tests. MS is known to be a chronic autoimmune progressive disease of the central nervous system of multifactor origin that is very common in regions with cold and humid climate. Disorder of thermoregulation caused by autonomic dysfunction is a typical feature of MS, however the role of the cold in the disease development is still underestimated. Methods. Thirty two MS patients (17 males, 15 females, mean age 29,6 ± 4,2 years) with the remittent form of the disease (mean disease duration 4,2 ± 2,7 years) and 18 age-matched healthy controls volunteered to participate in this study. Susceptibility to cold was analyzed with the use of visual-analogous scale. The duration of cold-induced vasoconstriction after local cold test was estimated using by infrared thermometry. Autonomic regulation of vasomotor reactions was investigated with the help of the skin sympathetic response (SSR) analysis. Results. The analysis of self-reported perception of the cold in MS patients showed their low tolerance to cold. Slow recovery of the skin temperature of the hand in the local cold test observed in MS patients was considered as the aggravated cold-induced vasoconstriction. The decreased SSR in the hands and feet in MS patients was found that indicates the deficit of the neurogenic control of thermoregulatory vasomotor reactions. Conclusion. The results obtained demonstrate the impairment of thermoregulation under cold in MS patients that leads to higher individual susceptibility to cold of this group. Comparing of the data found in this study on the mechanisms of the individual cold-induced reactivity in MS patients with epidemiological surveys enable to conclude that cold environment has potential modulating effect of on the course of MS.

scholarly journals Additive Manufacturing of Astragaloside-Containing Polyurethane Nerve Conduits Influenced Schwann Cell Inflammation and Regeneration

Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 353
Author(s):  
Yueh-Sheng Chen ◽  
Shih-Sheng Chang ◽  
Hooi Yee Ng ◽  
Yu-Xuan Huang ◽  
Chien-Chang Chen ◽  
...  
Keyword(s):  
Nervous System ◽  
Cellular Proliferation ◽  
Neural Regeneration ◽  
Nerve Grafting ◽  
Necrosis Factor Alpha ◽  
Digital Light Processing ◽  
Nerve Conduits ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Factor Alpha

The peripheral nervous system is the bridge of communication between the central nervous system and other body systems. Autologous nerve grafting is the mainstream method for repair of nerve lesions greater than 20 mm. However, there are several disadvantages and limitations of autologous nerve grafting, thus prompting the need for fabrication of nerve conduits for clinical use. In this study, we successfully fabricated astragaloside (Ast)-containing polyurethane (PU) nerve guidance conduits via digital light processing, and it was noted that the addition of Ast improved the hydrophilicity of traditional PU conduits by at least 23%. The improved hydrophilicity not only led to enhanced cellular proliferation of rat Schwann cells, we also noted that levels of inflammatory markers tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) significantly decreased with increasing concentrations of Ast. Furthermore, the levels of neural regeneration markers were significantly enhanced with the addition of Ast. This study demonstrated that Ast-containing PU nerve conduits can be potentially used as an alternative solution to regenerate peripheral nerve injuries.

scholarly journals CD69 Targeting Enhances Anti-vaccinia Virus Immunity

2019 ◽  
Vol 93 (19) ◽  
Author(s):  
Laura Notario ◽  
Jennifer Redondo-Antón ◽  
Elisenda Alari-Pahissa ◽  
Almudena Albentosa ◽  
Magdalena Leiva ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Vaccinia Virus ◽  
Immune Cells ◽  
Nk Cell ◽  
Mtor Signaling ◽  
Cell Reactivity ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha

ABSTRACT CD69 is highly expressed on the leukocyte surface upon viral infection, and its regulatory role in the vaccinia virus (VACV) immune response has been recently demonstrated using CD69−/− mice. Here, we show augmented control of VACV infection using the anti-human CD69 monoclonal antibody (MAb) 2.8 as both preventive and therapeutic treatment for mice expressing human CD69. This control was related to increased natural killer (NK) cell reactivity and increased numbers of cytokine-producing T and NK cells in the periphery. Moreover, similarly increased immunity and protection against VACV were reproduced over both long and short periods in anti-mouse CD69 MAb 2.2-treated immunocompetent wild-type (WT) mice and immunodeficient Rag2−/− CD69+/+ mice. This result was not due to synergy between infection and anti-CD69 treatment since, in the absence of infection, anti-human CD69 targeting induced immune activation, which was characterized by mobilization, proliferation, and enhanced survival of immune cells as well as marked production of several innate proinflammatory cytokines by immune cells. Additionally, we showed that the rapid leukocyte effect induced by anti-CD69 MAb treatment was dependent on mTOR signaling. These properties suggest the potential of CD69-targeted therapy as an antiviral adjuvant to prevent derived infections. IMPORTANCE In this study, we demonstrate the influence of human and mouse anti-CD69 therapies on the immune response to VACV infection. We report that targeting CD69 increases the leukocyte numbers in the secondary lymphoid organs during infection and improves the capacity to clear the viral infection. Targeting CD69 increases the numbers of gamma interferon (IFN-γ)- and tumor necrosis factor alpha (TNF-α)-producing NK and T cells. In mice expressing human CD69, treatment with an anti-CD69 MAb produces increases in cytokine production, survival, and proliferation mediated in part by mTOR signaling. These results, together with the fact that we have mainly worked with a human-CD69 transgenic model, reveal CD69 as a treatment target to enhance vaccine protectiveness.

scholarly journals Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Science ◽  
2019 ◽  
Vol 365 (6460) ◽  
pp. eaav7188 ◽  
Author(s):  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Expression Profiles ◽  
Human Microglia ◽  
Histocompatibility Complex ◽  
The Central Nervous System ◽  
Reference Map ◽  
Peripheral Immune Cells ◽  
Genomic Map ◽  
Cellular Components

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

scholarly journals Fair data for next-generation management of multiple sclerosis

2017 ◽  
Vol 24 (9) ◽  
pp. 1151-1156 ◽  
Author(s):  
Liesbet M Peeters
Keyword(s):  
Multiple Sclerosis ◽  
Multidisciplinary Treatment ◽  
Treatment Strategies ◽  
Population Based ◽  
Disease Modifying Drugs ◽  
Disease Epidemiology ◽  
Individual Level ◽  
Precision Level ◽  
The Central Nervous System ◽  
The Individual

Multiple sclerosis (MS) is a progressive demyelinating and degenerative disease of the central nervous system with symptoms depending on the disease type and the site of lesions and is featured by heterogeneity of clinical expressions and responses to treatment strategies. An individualized clinical follow-up and multidisciplinary treatment is required. Transforming the population-based management of today into an individualized, personalized and precision-level management is a major goal in research. Indeed, a complex and unique interplay between genetic background and environmental exposure in each case likely determines clinical heterogeneity. To reach insights at the individual level, extensive amount of data are required. Many databases have been developed over the last few decades, but access to them is limited, and data are acquired in different ways and differences in definitions and indexing and software platforms preclude direct integration. Most existing (inter)national registers and IT platforms are strictly observational or focus on disease epidemiology or access to new disease modifying drugs. Here, a method to revolutionize management of MS to a personalized, individualized and precision level is outlined. The key to achieve this next level is FAIR data.

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