scholarly journals Astroglial and Microglial Purinergic P2X7 Receptor as a Major Contributor to Neuroinflammation during the Course of Multiple Sclerosis

2021 ◽  
Vol 22 (16) ◽  
pp. 8404
Author(s):  
Marta Sidoryk-Węgrzynowicz ◽  
Lidia Strużyńska
Keyword(s):  
Multiple Sclerosis ◽  
Inflammatory Reaction ◽  
P2x7 Receptor ◽  
Purinergic Signaling ◽  
Causative Factor ◽  
P2x7 Receptors ◽  
Autoimmune Inflammatory Disease ◽  
Demyelinating Lesions ◽  
Purinergic P2x7 Receptor ◽  
The Central Nervous System

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system that leads to the progressive disability of patients. A characteristic feature of the disease is the presence of focal demyelinating lesions accompanied by an inflammatory reaction. Interactions between autoreactive immune cells and glia cells are considered as a central mechanism underlying the pathology of MS. A glia-mediated inflammatory reaction followed by overproduction of free radicals and generation of glutamate-induced excitotoxicity promotes oligodendrocyte injury, contributing to demyelination and subsequent neurodegeneration. Activation of purinergic signaling, in particular P2X7 receptor-mediated signaling, in astrocytes and microglia is an important causative factor in these pathological processes. This review discusses the role of astroglial and microglial cells, and in particular glial P2X7 receptors, in inducing MS-related neuroinflammatory events, highlighting the importance of P2X7R-mediated molecular pathways in MS pathology and identifying these receptors as a potential therapeutic target.

Recent advances on immunosuppressive drugs and remyelination enhancers for the treatment of multiple sclerosis

2021 ◽  
Vol 27 ◽  
Author(s):  
Jennifer Cadenas-Fernández ◽  
Pablo Ahumada-Pascual ◽  
Luis Sanz Andreu ◽  
Ana Velasco
Keyword(s):  
Multiple Sclerosis ◽  
Intracellular Signaling ◽  
Demyelinating Disease ◽  
Lipid Synthesis ◽  
Immunosuppressive Drugs ◽  
Nerve Fibers ◽  
Myelin Sheaths ◽  
Demyelinating Lesions ◽  
The Central Nervous System ◽  
Lipid Structures

: Mammalian nervous systems depend crucially on myelin sheaths covering the axons. In the central nervous system, myelin sheaths consist of lipid structures which are generated from the membrane of oligodendrocytes (OL). These sheaths allow fast nerve transmission, protect axons and provide them metabolic support. In response to specific traumas or pathologies, these lipid structures can be destabilized and generate demyelinating lesions. Multiple sclerosis (MS) is an example of a demyelinating disease in which the myelin sheaths surrounding the nerve fibers of the brain and spinal cord are damaged. MS is the leading cause of neurological disability in young adults in many countries, and its incidence has been increasing in recent decades. Related to its etiology, it is known that MS is an autoimmune and inflammatory CNS disease. However, there are no effective treatments for this disease and the immunomodulatory therapies that currently exist have proven limited success since they only delay the progress of the disease. Nowadays, one of the main goals in the MS research is to find treatments which allows the recovery of neurological disabilities due to demyelination. To this end, different approaches, such as modulating intracellular signaling or regulating the lipid metabolism of OLs, are being considered. Here, in addition to immunosuppressive or immunomodulatory drugs that reduce the immune response against myelin sheaths, we review a diverse group of drugs that promotes endogenous remyelination in MS patients and whose use may be interesting as potential therapeutic agents in MS disease. To this end, we compile specific treatments against MS that are currently in the market with remyelination strategies which have entered into human clinical trials for future reparative MS therapies. The method used in this study is a systematic literature review on PubMed, Web of Science and Science Direct databases up to May 31, 2020. To narrow down the search results in databases, more specific keywords, such as, “myelin sheath”, “remyelination”, “demyelination”, “oligodendrocyte” and “lipid synthesis” were used to focus the search. We favoured papers published after January, 2015, but did not exclude earlier seminal papers.

scholarly journals Impact of Exercise on Immunometabolism in Multiple Sclerosis

2020 ◽  
Vol 9 (9) ◽  
pp. 3038 ◽  
Author(s):  
Remsha Afzal ◽  
Jennifer K Dowling ◽  
Claire E McCoy
Keyword(s):  
Multiple Sclerosis ◽  
Cell Function ◽  
Immune Cell ◽  
Therapeutic Benefits ◽  
Demyelinating Lesions ◽  
Inflammatory State ◽  
Autoimmune Condition ◽  
The Central Nervous System ◽  
Axonal Degradation

Multiple Sclerosis (MS) is a chronic, autoimmune condition characterized by demyelinating lesions and axonal degradation. Even though the cause of MS is heterogeneous, it is known that peripheral immune invasion in the central nervous system (CNS) drives pathology at least in the most common form of MS, relapse-remitting MS (RRMS). The more progressive forms’ mechanisms of action remain more elusive yet an innate immune dysfunction combined with neurodegeneration are likely drivers. Recently, increasing studies have focused on the influence of metabolism in regulating immune cell function. In this regard, exercise has long been known to regulate metabolism, and has emerged as a promising therapy for management of autoimmune disorders. Hence, in this review, we inspect the role of key immunometabolic pathways specifically dysregulated in MS and highlight potential therapeutic benefits of exercise in modulating those pathways to harness an anti-inflammatory state. Finally, we touch upon current challenges and future directions for the field of exercise and immunometabolism in MS.

scholarly journals Hypoperfusion of the Cerebral White Matter in Multiple Sclerosis: Possible Mechanisms and Pathophysiological Significance

2008 ◽  
Vol 28 (10) ◽  
pp. 1645-1651 ◽  
Author(s):  
Jacques De Keyser ◽  
Christel Steen ◽  
Jop P Mostert ◽  
Marcus W Koch
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Adrenergic Receptors ◽  
Perfusion Magnetic Resonance Imaging ◽  
Cerebral White Matter ◽  
Perivascular Spaces ◽  
Axonal Loss ◽  
Normal Appearing White Matter ◽  
Demyelinating Lesions ◽  
The Central Nervous System

Multiple sclerosis (MS) is a disease of the central nervous system characterized by patchy areas of demyelination, inflammation, axonal loss and gliosis, and a diffuse axonal degeneration throughout the so-called normal-appearing white matter (NAWM). A number of recent studies using perfusion magnetic resonance imaging in both relapsing and progressive forms of MS have shown a decreased perfusion of the NAWM, which does not appear to be secondary to axonal loss. The reduced perfusion of the NAWM in MS might be caused by a widespread astrocyte dysfunction, possibly related to a deficiency in astrocytic β2-adrenergic receptors and a reduced formation of cAMP, resulting in a reduced uptake of K+ at the nodes of Ranvier and a reduced release of K+ in the perivascular spaces. Pathologic and imaging studies suggest that ischemic changes might be involved in the development of a subtype of focal demyelinating lesions (type III lesions), and there appears to exist a relationship between decreased white matter perfusion and cognitive dysfunction in patients with MS.

scholarly journals Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Genaro G. Ortiz ◽  
Fermín P. Pacheco-Moisés ◽  
Oscar K. Bitzer-Quintero ◽  
Ana C. Ramírez-Anguiano ◽  
Luis J. Flores-Alvarado ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Tissue Injury ◽  
Autoimmune Disorder ◽  
Demyelinating Lesions ◽  
The Central Nervous System ◽  
The Brain ◽  
And Oxidative Stress

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle.

scholarly journals Multiple Sclerosis Revealed by Anterior Uveitis

2020 ◽  
Vol 2 (5) ◽  
Author(s):  
Sidi Dahi ◽  
Mehdi Khamaily ◽  
Joumany Brahim Salem ◽  
Imane Tarib ◽  
Mounia Bouchaar ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Inflammatory Disease ◽  
Anterior Uveitis ◽  
Oculomotor Nerve ◽  
Ocular Involvement ◽  
Atypical Case ◽  
Autoimmune Inflammatory Disease ◽  
The Central Nervous System

Multiple sclerosis is an autoimmune inflammatory disease of the central nervous system, leading to the formation of foci of demyelination. Ocular involvement is quite frequent and multiple, dominated by inflammatory optic neuropathies, oculomotor nerve damage, nystagmus and uveitis. We report an atypical case of multiple sclerosis revealed by an anterior unilateral synechiatic hypertensive uveitis in a young patient of 27 years.

scholarly journals Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data

2021 ◽  
Vol 12 ◽  
Author(s):  
Yijie He ◽  
Lin Huang ◽  
Yaqin Tang ◽  
Zeyuan Yang ◽  
Zhijie Han
Keyword(s):  
Multiple Sclerosis ◽  
Transcription Initiation ◽  
Gene Interaction ◽  
Initiation Site ◽  
Rna Seq ◽  
Average Percentage ◽  
Genome Wide ◽  
Variant Genotype ◽  
Demyelinating Lesions ◽  
The Central Nervous System

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelinating lesions in the central nervous system. Recently, the dysregulation of alternative splicing (AS) in the brain has been found to significantly influence the progression of MS. Moreover, previous studies demonstrate that many MS-related variants in the genome act as the important regulation factors of AS events and contribute to the pathogenesis of MS. However, by far, no genome-wide research about the effect of genomic variants on AS events in MS has been reported. Here, we first implemented a strategy to obtain genomic variant genotype and AS isoform average percentage spliced-in values from RNA-seq data of 142 individuals (51 MS patients and 91 controls). Then, combing the two sets of data, we performed a cis-splicing quantitative trait loci (sQTLs) analysis to identify the cis-acting loci and the affected differential AS events in MS and further explored the characteristics of these cis-sQTLs. Finally, the weighted gene coexpression network and gene set enrichment analyses were used to investigate gene interaction pattern and functions of the affected AS events in MS. In total, we identified 5835 variants affecting 672 differential AS events. The cis-sQTLs tend to be distributed in proximity of the gene transcription initiation site, and the intronic variants of them are more capable of regulating AS events. The retained intron AS events are more susceptible to influence of genome variants, and their functions are involved in protein kinase and phosphorylation modification. In summary, these findings provide an insight into the mechanism of MS.

scholarly journals Learning a CNN on multiple sclerosis lesion segmentation with self-supervision

2020 ◽  
Vol 2020 (17) ◽  
pp. 3-1-3-7
Author(s):  
Alexandre Fenneteau ◽  
Pascal Bourdon ◽  
David Helbert ◽  
Christine Fernandez-Maloigne ◽  
Christophe Habas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Multiple Sclerosis Lesion ◽  
Image Size ◽  
Mr Images ◽  
Traffic Sign ◽  
Demyelinating Lesions ◽  
The Central Nervous System ◽  
Pros And Cons ◽  
Segmentation Task ◽  
High Level

Multiple Sclerosis (MS) is a chronic, often disabling, autoimmune disease affecting the central nervous system and characterized by demyelination and neuropathic alterations. Magnetic Resonance (MR) images plays a pivotal role in the diagnosis and the screening of MS. MR images identify and localize demyelinating lesions (or plaques) and possible associated atrophic lesions whose MR aspect is in relation with the evolution of the disease. We propose a novel MS lesions segmentation method for MR images, based on Convolutional Neural Networks (CNNs) and partial self-supervision and studied the pros and cons of using self-supervision for the current segmentation task. Investigating the transferability by freezing the firsts convolutional layers, we discovered that improvements are obtained when the CNN is retrained from the first layers. We believe such results suggest that MRI segmentation is a singular task needing high level analysis from the very first stages of the vision process, as opposed to vision tasks aimed at day-to-day life such as face recognition or traffic sign classification. The evaluation of segmentation quality has been performed on full image size binary maps assembled from predictions on image patches from an unseen database.

scholarly journals Current Advances in Pediatric Onset Multiple Sclerosis

Biomedicines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 71 ◽  
Author(s):  
Kristen S. Fisher ◽  
Fernando X. Cuascut ◽  
Victor M. Rivera ◽  
George J. Hutton
Keyword(s):  
Multiple Sclerosis ◽  
Current Knowledge ◽  
Pediatric Population ◽  
Treatment Patterns ◽  
Time Treatment ◽  
Disease Modifying Therapies ◽  
Autoimmune Inflammatory Disease ◽  
Significant Disability ◽  
The Central Nervous System ◽  
Over Time

Multiple sclerosis (MS) is an autoimmune inflammatory disease affecting the central nervous system leading to demyelination. MS in the pediatric population is rare, but has been shown to lead to significant disability over the duration of the disease. As we have learned more about pediatric MS, there has been a development of improved diagnostic criteria leading to earlier diagnosis, earlier initiation of disease-modifying therapies (DMT), and an increasing number of DMT used in the treatment of pediatric MS. Over time, treatment with DMT has trended towards the initiation of higher efficacy treatment at time of diagnosis to help prevent further disease progression and accrual of disability over time, and there is evidence in current literature that supports this change in treatment patterns. In this review, we discuss the current knowledge in diagnosis, treatment, and clinical outcomes in pediatric MS.

scholarly journals Case Report: Persisting Lymphopenia During Neuropsychiatric Tumefactive Multiple Sclerosis Rebound Upon Fingolimod Withdrawal

2021 ◽  
Vol 12 ◽  
Author(s):  
Valeria Koska ◽  
Moritz Förster ◽  
Katja Brouzou ◽  
Ercan Arat ◽  
Philipp Albrecht ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Opportunistic Infections ◽  
Neuropsychiatric Symptoms ◽  
Severe Disease ◽  
Mass Effect ◽  
Disease Modifying Therapy ◽  
Perifocal Edema ◽  
Demyelinating Lesions ◽  
The Central Nervous System ◽  
Relapsing Remitting Multiple Sclerosis

Fingolimod (FTY) is a disease modifying therapy for relapsing remitting multiple sclerosis (RRMS) which can lead to severe lymphopenia requiring therapy discontinuation in order to avoid adverse events. However, this can result in severe disease reactivation occasionally presenting with tumefactive demyelinating lesions (TDLs). TDLs, which are thought to originate from a massive re-entry of activated lymphocytes into the central nervous system, are larger than 2 cm in diameter and may feature mass effect, perifocal edema, and gadolinium enhancement. In these cases, it can be challenging to exclude important differential diagnoses for TDLs such as progressive multifocal leukoencephalopathy (PML) or other opportunistic infections. Here, we present the case of a 26-year-old female patient who suffered a massive rebound with TDLs following FTY discontinuation with primarily neuropsychiatric symptoms despite persisting lymphopenia. Two cycles of seven plasmaphereses each were necessary to achieve remission and ocrelizumab was used for long-term stabilization.

Tumor-Like Multiple Sclerosis: Report of Four Cases and Literature Review

2006 ◽  
Vol 92 (6) ◽  
pp. 559-562 ◽  
Author(s):  
Emanuela Caroli ◽  
Maurizio Salvati ◽  
Luigi Ferrante
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Demyelinating Disease ◽  
Brain Lesion ◽  
Mri Scan ◽  
Cerebral Tumor ◽  
Demyelinating Lesions ◽  
The Central Nervous System ◽  
Demyelinating Process

Aims and background Classical multiple sclerosis plaques usually have typical features on gadolinium-enhanced MRI scan. This non-neoplastic demyelinating process of the central nervous system generally does not produce focal space-occupying lesions associated with ring enhancement. However, atypical appearance of demyelinating lesions simulating a brain tumor is a possible well-known phenomenon. Methods We present our experience with 4 cases of multiple sclerosis indistinguishable clinically and neuroradiologically from a cerebral tumor. All patients underwent surgery. Results Histological examinations of all cases were positive for multiple sclerosis plaques. Conclusions The presented cases demonstrate the importance of considering a demyelinating disease in the differential diagnosis of a tumor-like brain lesion.

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