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1.
Zhen Ci Yan Jiu ; 45(1): 1-7, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144901

RESUMO

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in accelerating the aggregation of microglia and promoting the remyelination at the location of demyelination. METHODS: C57BL/6 mice were randomly divided into 4 groups: normal, control, model (LPC) and LPC+EA. The demyelination model was established by microinjection of Lysolecithin (LPC, 1 µL) into the left corpus callosum. EA (2 Hz/15 Hz, 2-4 mA) was applied to "Baihui"(GV20)and "Zhiyang"(GV9)for 30 min,once daily for 3 days, then, once every other day for 18 days. Immuno-fluorescence staining was used to observe the expression of myelin basic protein (MBP) and Axl tyrosine kinase receptor (Axl), Iba1 and numbers of Olig2-positive oligodendrocytes in the corpus callosum. Western blot was employed to detect the expression of MBP in the corpus callosum, and Oil Red O staining was used to observe changes of number of myelin pieces. RESULTS: Following modeling, the expression levels of MBP on day 5 and 10 after modeling were significantly decreased (P<0.05, P<0.01), Iba1 expression and Olig2-positive oligodendrocyte numbers on day 10 apparently increased (P<0.001, P<0.01). On day 21 after modeling, the levels of the above mentioned indexes returned to normal. After EA intervention, the levels of MBP expression on day 5 and 10, Axl, Iba1 protein expression and Olig2-positive oligodendrocyte numbers on day 5 were markedly increased (P<0.001,P<0.01,P<0.05), while Iba1 expression on day 10 was considerably decreased in comparison with the model group (P<0.01).Oil Red O staining showed that on day 5 after modeling, the number of red lipid droplets were obviously increased in the corpus callosum tissue on the injection side, and apparently reduced in the EA group, suggesting a clearance of the accumulated myelin fragments by EA. CONCLUSION: EA intervention may reduce myelin debris and promote the aggregation of microglial cells and oligodendrocytes to the injured site, accelerate the myelin regeneration and up-regulate the expression of MBP and Axl of corpus callosum in demyelination mice.


Assuntos
Doenças Desmielinizantes , Eletroacupuntura , Animais , Corpo Caloso , Camundongos , Camundongos Endogâmicos C57BL , Bainha de Mielina
3.
Neuron ; 105(2): 293-309.e5, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31901304

RESUMO

The molecular mechanisms that govern the maturation of oligodendrocyte lineage cells remain unclear. Emerging studies have shown that N6-methyladenosine (m6A), the most common internal RNA modification of mammalian mRNA, plays a critical role in various developmental processes. Here, we demonstrate that oligodendrocyte lineage progression is accompanied by dynamic changes in m6A modification on numerous transcripts. In vivo conditional inactivation of an essential m6A writer component, METTL14, results in decreased oligodendrocyte numbers and CNS hypomyelination, although oligodendrocyte precursor cell (OPC) numbers are normal. In vitro Mettl14 ablation disrupts postmitotic oligodendrocyte maturation and has distinct effects on OPC and oligodendrocyte transcriptomes. Moreover, the loss of Mettl14 in oligodendrocyte lineage cells causes aberrant splicing of myriad RNA transcripts, including those that encode the essential paranodal component neurofascin 155 (NF155). Together, our findings indicate that dynamic RNA methylation plays an important regulatory role in oligodendrocyte development and CNS myelination.


Assuntos
Adenosina/análogos & derivados , Diferenciação Celular/fisiologia , Metiltransferases/fisiologia , Bainha de Mielina/fisiologia , Oligodendroglia/citologia , Oligodendroglia/fisiologia , RNA Mensageiro/metabolismo , Adenosina/metabolismo , Animais , Moléculas de Adesão Celular/metabolismo , Contagem de Células , Linhagem da Célula , Células Cultivadas , Feminino , Masculino , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos , Camundongos Transgênicos , Fatores de Crescimento Neural/metabolismo , Células Precursoras de Oligodendrócitos/fisiologia
4.
Cancer Immunol Immunother ; 69(2): 245-253, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31676924

RESUMO

Schwann cells are the principal glial cells of the peripheral nervous system which maintain neuronal homeostasis. Schwann cells support peripheral nerve functions and play a critical role in many pathological processes including injury-induced nerve repair, neurodegenerative diseases, infections, neuropathic pain and cancer. Schwann cells are implicated in a wide range of diseases due, in part, to their ability to interact and modulate immune cells. We discuss the accumulating examples of how Schwann cell regulation of the immune system initiates and facilitates the progression of various diseases. Furthermore, we highlight how Schwann cells may orchestrate an immunosuppressive tumor microenvironment by polarizing and modulating the activity of the dendritic cells.


Assuntos
Suscetibilidade a Doenças , Imunomodulação , Células de Schwann/imunologia , Células de Schwann/metabolismo , Animais , Biomarcadores , Humanos , Bainha de Mielina/imunologia , Bainha de Mielina/metabolismo , Transdução de Sinais
5.
Life Sci ; 241: 117102, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31790691

RESUMO

Peripheral nerve injuries are common conditions that often lead to dysfunctions. Although much knowledge exists on the several factors that mediate the complex biological process involved in peripheral nerve regeneration, there is a lack of effective treatments that ensure full functional recovery. Naringenin (NA) is the most abundant flavanone found in citrus fruits and it has promising neuroprotective, anti-inflammatory and antioxidant effects. This study aimed to enhance peripheral nerve regeneration using an inclusion complex containing NA and hydroxypropyl-ß-cyclodextrin (HPßCD), named NA/HPßCD. A mouse sciatic nerve crush model was used to evaluate the effects of NA/HPßCD on nerve regeneration. Sensory and motor parameters, hyperalgesic behavior and the sciatic functional index (SFI), respectively, improved with NA treatment. Western blot analysis revealed that the levels of p75NTR ICD and p75NTR full length as well phospho-JNK/total JNK ratios were preserved by NA treatment. In addition, NA treatment was able to decrease levels of caspase 3. The concentrations of TNF-α and IL-1ß were decreased in the lumbar spine, on the other hand there was an increase in IL-10. NA/HPßCD presented a better overall morphological profile but it was not able to increase the number of myelinated fibers. Thus, NA was able to enhance nerve regeneration, and NA/HPßCD decreased effective drug doses while maintaining the effect of the pure drug, demonstrating the advantage of using the complex over the pure compound.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Flavanonas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Nervo Isquiático/fisiologia , Animais , Hiperalgesia/tratamento farmacológico , Interleucina-10/metabolismo , Masculino , Camundongos , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Regeneração Nervosa/fisiologia , Medição da Dor , Receptores de Fator de Crescimento Neural/antagonistas & inibidores , Receptores de Fator de Crescimento Neural/metabolismo , Recuperação de Função Fisiológica , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/lesões , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
6.
Cell Mol Life Sci ; 77(1): 161-177, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31161284

RESUMO

Peripheral nervous system development involves a tight coordination of neuronal birth and death and a substantial remodelling of the myelinating glia cytoskeleton to achieve myelin wrapping of its projecting axons. However, how these processes are coordinated through time is still not understood. We have identified engulfment and cell motility 1, Elmo1, as a novel component that regulates (i) neuronal numbers within the Posterior Lateral Line ganglion and (ii) radial sorting of axons by Schwann cells (SC) and myelination in the PLL system in zebrafish. Our results show that neuronal and myelination defects observed in elmo1 mutant are rescued through small GTPase Rac1 activation. Inhibiting macrophage development leads to a decrease in neuronal numbers, while peripheral myelination is intact. However, elmo1 mutants do not show defective macrophage activity, suggesting a role for Elmo1 in PLLg neuronal development and SC myelination independent of macrophages. Forcing early Elmo1 and Rac1 expression specifically within SCs rescues elmo1-/- myelination defects, highlighting an autonomous role for Elmo1 and Rac1 in radial sorting of axons by SCs and myelination. This uncovers a previously unknown function of Elmo1 that regulates fundamental aspects of PNS development.


Assuntos
Bainha de Mielina/metabolismo , Neurogênese , Neurônios/citologia , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/crescimento & desenvolvimento , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Apoptose , Axônios/metabolismo , Axônios/ultraestrutura , Movimento Celular , Neurônios/metabolismo , Neurônios/ultraestrutura , Nervos Periféricos/crescimento & desenvolvimento , Nervos Periféricos/ultraestrutura , Células de Schwann/citologia , Células de Schwann/metabolismo , Células de Schwann/ultraestrutura
7.
Arch Ital Biol ; 157(2-3): 76-88, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31821531

RESUMO

Ultrastructural evaluation of myelin coat helps to understand the possible background of pathological changes leading to deterioration or complete loss of nerve functions. A number of terms were previously introduced to describe the fine structural changes in myelin under various conditions. We believe that using a common terminology will be helpful to interpret the structure/function relationship in neurological disorders empowering the diagnosis and possible therapeutical approaches. In this paper, we present examples of ultrastructural changes in myelin during myelination, demyelination, re-myelination and dysmyelination processes and we reviewed the terminology previously used.We tried to include all studies reporting ultrastructural findings with no limitation to the experimental conditions, the species used and the disorders. The terminology used to describe the structural findings included compacted myelin, partially compacted myelin, noncompacted myelin, redundancy (hypermyelination, tomacula, myelinosome), splitting, complete circular splitting, myelin degradation, concentric lamellar bodies (myelin figures), loss of myelin lamellae, polyaxonal Schwann cells and necrotic cell debris.Ultrastructural data described in this paper aimed to provide a guide for future studies. We concluded that the evaluation of ultrastructural changes in any neurological disorder is greatly valuable for a better understanding of pathological and physiological changes occured. We also believe that supporting the ultrastructural findings with quantitative methods in the future will be of great value.


Assuntos
Bainha de Mielina , Células de Schwann , Terminologia como Assunto
8.
Adv Exp Med Biol ; 1190: 3-22, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760634

RESUMO

Increasing studies have demonstrated multiple signaling molecules responsible for oligodendrocytes and Schwann cells development such as migration, differentiation, myelination, and axo-glial interaction. However, complicated roles in these events are still poorly understood. This chapter focuses on well established intracellular signaling transduction and recent topics that control myelination and are elucidated from accumulating evidences. The underlying molecular mechanisms, which involved in membrane trafficking through small GTPase Arf6 and its activator cytohesins, demonstrate the crosstalk between well established intracellular signaling transduction and a new finding signaling pathway in glial cells links to physiological phenotype and essential role in peripheral nerve system (PNS). Since Arf family proteins affect the expression levels of myelin protein zero (MPZ) and Krox20, which is a transcription factor regulatory factor in early developmental stages of Schwann cells, Arf proteins likely to be key regulator for Schwann cells development. Herein, we discuss how intracellular signaling transductions in Schwann cells associate with myelination in CNS and PNS.


Assuntos
Remielinização , Células de Schwann/fisiologia , Transdução de Sinais , Humanos , Bainha de Mielina/fisiologia , Neuroglia/fisiologia , Oligodendroglia/fisiologia
9.
Adv Exp Med Biol ; 1190: 23-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760635

RESUMO

Regulation of differentiation and proliferation of Schwann cells is an essential part of the regulation of peripheral nerve development, degeneration, and regeneration. ZNRF1, a ubiquitin ligase, is expressed in undifferentiated/repair Schwann cells, directs glutamine synthetase to proteasomal degradation, and thereby increase glutamate levels in Schwann cell environment. Glutamate elicits subcellular signaling in Schwann cells via mGluR2 to modulate Neuregulin-1/ErbB2/3 signaling and thereby promote undifferentiated phenotype of Schwann cell.


Assuntos
Ácido Glutâmico/fisiologia , Bainha de Mielina/fisiologia , Nervos Periféricos/fisiologia , Transdução de Sinais , Proteínas de Transporte/fisiologia , Diferenciação Celular , Humanos , Receptores de AMPA/fisiologia , Células de Schwann
10.
Adv Exp Med Biol ; 1190: 33-42, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760636

RESUMO

Myelination and remyelination in the central nervous system (CNS) are essential for rapid conduction of action potentials and for appropriate neuronal communications supporting higher brain functions. Myelination is dependent on developmental stage and is controlled by neuronal axons-oligodendrocyte (OL) signaling. Numerous studies of the initial myelination and remyelination stages in the CNS have demonstrated several key cytoskeletal signals in axons and OLs. In this review, we focus on cytoskeletal signal-regulated OL myelination and remyelination, with particular attention to neuronal Notch proteins, bidirectional Eph/ephrin signaling, OL integrin and cadherin superfamily proteins, OL actin rearrangement, and OL tyrosine kinase Fyn substrate proteins during the initial myelination and remyelination stages in the CNS.


Assuntos
Citoesqueleto/fisiologia , Oligodendroglia/fisiologia , Remielinização , Transdução de Sinais , Sistema Nervoso Central/fisiologia , Efrinas/fisiologia , Humanos , Bainha de Mielina/fisiologia , Receptores Notch/fisiologia
11.
Adv Exp Med Biol ; 1190: 43-51, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760637

RESUMO

Oligodendrocyte form myelin around the axons to regulate the conduction velocity. Myelinated axons are composed of white matter to act as cables to connect distinct brain regions. Recent human MRI studies showed that the signal from white matter change in the people with special skills such as taxi driver, piano player, and juggling. The change of the white matter suggested that (1) The plasticity of myelination depends on neuronal activity (activity-dependent myelination) and (2) White matter plasticity is essential for brain functions. In this session, we discussed that how the un-electrical components, oligodendrocytes, and its precursor cells receive the signal from electrically active neurons and differentiate, proliferate, and myelinate the axons to modulate the activity of neuronal circuits, ultimately affect on their behaviors. In this review, we highlight the physiological functions of oligodendrocyte and their neuronal activity-dependent functions and thus show new insight for their contribution to brain functions.


Assuntos
Bainha de Mielina/fisiologia , Oligodendroglia/fisiologia , Substância Branca/fisiologia , Axônios/fisiologia , Humanos , Neurônios/fisiologia
12.
Adv Exp Med Biol ; 1190: 53-62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760638

RESUMO

While oligodendrocytes have been thought to be homogenous, a number of reports have indicated evidences of the heterogeneity of oligodendrocytes and their precursor cells, OPCs. Almost a century ago, Del Río Hortega found three and four types of oligodendrocytes with regions where they exist and their morphologies, respectively. Interfascicular oligodendrocytes are one of the three regional dependent types and are the most typical oligodendendroglial cells that myelinate axonal fibers in the white matter tracts. In the other two, perineuronal oligodendrocyes function as reserve cells for remyelination and regulate neuronal excitability, whereas perivascular oligodendrocytes may play a role in metabolic support of axons. Among the four morphological categories, type I and II oligodendrocytes form many myelin sheaths on small-diameter axons and specific signal is required for the myelination of small-diameter axons. Type III and IV oligodendrocytes myelinate a few number of axons/or one axon, whose diameters are large. A recent comprehensive gene expression analysis with single-cell RNA sequencing identifies six different populations in mature oligodendrocytes and only one population in OPCs. However, OPCs are not uniformed developmentally and regionally. Further, the capacity of OPC differentiation depends on the environments and conditions of the tissues. Taken together, oligodendrocytes and OPCs are diverse as the other cell types in the CNS. The orchestration of these cells with their specialized functions is critical for proper functioning of the CNS.


Assuntos
Sistema Nervoso Central/fisiologia , Bainha de Mielina/fisiologia , Oligodendroglia/fisiologia , Axônios/fisiologia , Diferenciação Celular , Humanos , Neurônios/fisiologia , Substância Branca/fisiologia
13.
Adv Exp Med Biol ; 1190: 85-106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760640

RESUMO

Nerve conduction in myelinated axons is a fascinating subject due to the intricate structure and complex properties of the axon and its relation to the equally complex Schwann cells surrounding it. This chapter first deals with normal functional aspects of voltage-gated ion channels in the axon and Schwann cell membranes as well as their related proteins. Next, the pathophysiological alterations that are induced by experimental studies to mimic and study neuropathic disorders in humans are discussed. Finally, a link is made with human neuropathies associated with antibodies against gangliosides, and the putative mechanisms of axonal degeneration in demyelinating neuropathies are discussed. Although this chapter is relevant to understand symptoms in human neuropathies, the reader is referred to Franssen and Straver (Muscle Nerve 49:4-20, 2014) for a review of translational and clinical studies in human patients.


Assuntos
Doenças Desmielinizantes/fisiopatologia , Bainha de Mielina/fisiologia , Condução Nervosa , Axônios/fisiologia , Humanos , Células de Schwann/fisiologia
14.
Adv Exp Med Biol ; 1190: 123-144, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760642

RESUMO

Oligodendrocytes enable saltatory conduction by forming a myelin sheath around axons, dramatically boosts action potential conduction velocity. In addition to this canonical function of oligodendrocytes, it is now known that oligodendrocytes can respond to neuronal activity and regulate axonal conduction. Importantly, white matter plasticity, including adaptive responses by oligodendrocytes, has been shown to be involved in learning and memory. In this chapter, the role of oligodendrocytes in axonal conduction and axonal excitability will be reviewed. Focus will be paid to the mechanisms through which oligodendrocytes, including perineuronal oligodendrocytes, facilitate and suppress axonal conduction.


Assuntos
Axônios/fisiologia , Condução Nervosa , Oligodendroglia/fisiologia , Humanos , Bainha de Mielina/fisiologia , Substância Branca/fisiologia
15.
Adv Exp Med Biol ; 1190: 145-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760643

RESUMO

Mitochondria play essential roles in neurons and abnormal functions of mitochondria have been implicated in neurological disorders including myelin diseases. Since mitochondrial functions are regulated and maintained by their dynamic behavior involving localization, transport, and fusion/fission, modulation of mitochondrial dynamics would be involved in physiology and pathology of myelinated axons. In fact, the integration of multimodal imaging in vivo and in vitro revealed that mitochondrial localization and transport are differentially regulated in nodal and internodal regions in response to the changes of metabolic demand in myelinated axons. In addition, the mitochondrial behavior in axons is modulated as adaptive responses to demyelination irrespective of the cause of myelin loss, and the behavioral modulation is partly through interactions with cytoskeletons and closely associated with the pathophysiology of demyelinating diseases. Furthermore, the behavior and functions of axonal mitochondria are modulated in congenital myelin disorders involving impaired interactions between axons and myelin-forming cells, and, together with the inflammatory environment, implicated in axonal degeneration and disease phenotypes. Further studies on the regulatory mechanisms of the mitochondrial dynamics in myelinated axons would provide deeper insights into axo-glial interactions mediated through myelin ensheathment, and effective manipulations of the dynamics may lead to novel therapeutic strategies protecting axonal and neuronal functions and survival in primary diseases of myelin.


Assuntos
Axônios/fisiologia , Doenças Desmielinizantes/fisiopatologia , Dinâmica Mitocondrial , Bainha de Mielina/fisiologia , Axônios/patologia , Humanos , Bainha de Mielina/patologia , Neurônios/patologia , Neurônios/fisiologia
16.
Adv Exp Med Biol ; 1190: 165-179, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760644

RESUMO

Myelin is heavily enriched in lipids (comprising approximately 70% of its dry weight), and the amount of cholesterol and glycolipids is higher than in any other cell membrane. Galactocerebroside (GalC) and its sulfated form, sulfatide, comprise the major glycolipid components of myelin. Their functional significance has been extensively studied using membrane models, cell culture, and in vivo experiments in which either GalC/sulfatide or sulfatide is deficient. From these studies, GalC and sulfatide have been distinctly localized within oligodendrocytes and their specific function in myelin has been elucidated. Here, the function of sulfatide in axo-glial interactions in myelin-forming cells as well as within myelin and its potential mechanisms of action are discussed.


Assuntos
Axônios/fisiologia , Bainha de Mielina/química , Neuroglia/fisiologia , Sulfoglicoesfingolipídeos/química , Humanos , Bainha de Mielina/fisiologia , Oligodendroglia/fisiologia
17.
Adv Exp Med Biol ; 1190: 181-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760645

RESUMO

Schmidt-Lanterman incisure (SLI) is a circular-truncated cone shape in the myelin internode that is a specific feature of myelinated nerve fibers formed in Schwann cells in the peripheral nervous system (PNS). The SLI circular-truncated cones elongate like spring at the narrow sites of beaded appearance nerve fibers under the stretched condition. In this chapter, we demonstrate various molecular complexes in SLI, and especially focus on membrane skeleton, protein 4.1G-membrane protein palmitoylated 6 (MPP6)-cell adhesion molecule 4 (CADM4). 4.1G was essential for the molecular targeting of MPP6 and CADM4 in SLI. Motor activity and myelin ultrastructures were abnormal in 4.1G-deficient mice, indicating the 4.1G function as a signal for proper formation of myelin in PNS. Thus, SLI probably has potential roles in the regulation of adhesion and signal transduction as well as in structural stability in Schwann cell myelin formation.


Assuntos
Bainha de Mielina/fisiologia , Sistema Nervoso Periférico/fisiologia , Células de Schwann/fisiologia , Animais , Axônios , Moléculas de Adesão Celular/fisiologia , Guanilato Quinases/fisiologia , Proteínas Ligadas a Lipídeos/fisiologia , Camundongos , Proteínas dos Microfilamentos/fisiologia , Bainha de Mielina/ultraestrutura , Transdução de Sinais
18.
Adv Exp Med Biol ; 1190: 201-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760646

RESUMO

Pelizaeus-Merzbacher disease (PMD) represents a group of disorders known as hypomyelinating leukodystrophies, which are characterized by abnormal development and maintenance of myelin in the central nervous system. PMD is caused by different types of mutations in the proteolipid protein 1 (PLP1) gene, which encodes a major myelin membrane lipoprotein. These mutations in the PLP1 gene result in distinct cellular and molecular pathologies and a spectrum of clinical phenotypes. In this chapter, I discuss the historical aspects and current understanding of the mechanisms underlying how different PLP1 mutations disrupt the normal process of myelination and result in PMD and other disorders.


Assuntos
Bainha de Mielina/patologia , Doença de Pelizaeus-Merzbacher/fisiopatologia , Humanos , Mutação , Proteína Proteolipídica de Mielina/genética , Doença de Pelizaeus-Merzbacher/genética , Fenótipo
19.
Adv Exp Med Biol ; 1190: 217-247, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760647

RESUMO

Multiple sclerosis (MS) is an inflammatory demyelinating disorder. Although all MS patients initially show a relapsing-remitting course, 20-50% subsequently enter a chronic progressive course at 10-20 years after onset that greatly influences their activities of daily living. There are 2.5 million MS patients worldwide with large regional and racial differences. In particular, there are many MS patients among Caucasians living in Europe, while the disease is relatively rare in Asians and Africans.Although MS is regarded as an autoimmune disease, many factors such as genetic background, environmental factors, and sex are involved in its pathogenesis. While the immunological mechanisms remain to be fully elucidated, invasion of autoreactive T cells into the central nervous system (CNS) tissue is considered the first step of the disease. These T cells react with myelin antigens and initiate demyelination of the CNS by activating cytotoxic T cells, macrophages, and B cells through the release of inflammatory cytokines. As a treatment option, disease-modifying therapies have recently been developed to prevent the recurrence of MS in addition to conventional treatment with corticosteroids for acute relapse. However, there are still few effective treatments for the chronic progressive phase, and it is thus imperative to decipher the mechanism for chronic progression.


Assuntos
Esclerose Múltipla/fisiopatologia , Linfócitos T/imunologia , Atividades Cotidianas , Linfócitos B/imunologia , Sistema Nervoso Central/fisiopatologia , Citocinas/imunologia , Humanos , Macrófagos/imunologia , Esclerose Múltipla/imunologia , Bainha de Mielina/imunologia
20.
Adv Exp Med Biol ; 1190: 249-256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760648

RESUMO

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) affecting more than two million people worldwide. As the exact etiology of MS remains elusive, the diagnosis of MS is made by referring to the McDonald diagnostic criteria, which utilizes MRI as a tool to identify "demyelinated" MS lesions. In particular, hyperintense lesions on T2-weighted images (T2WI) or so-called "T2-lesions" are considered to represent demyelinated MS lesions. T2WI, however, lacks myelin specificity, and moreover, remyelination could not be depicted by the use of such modality. For the accurate diagnosis and treatment decision-making, or for the future development of remyelination therapeutics, imaging tools to visualize myelin-specific signals are mandatory. In this chapter, the current use and the limitation of imaging modalities in MS diagnosis and treatment will be reviewed, with the introduction of new imaging method, namely q-space Myelin Map (qMM), to be used for visualization of demyelination and remyelination in MS.


Assuntos
Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/terapia , Bainha de Mielina/patologia , Humanos , Imagem por Ressonância Magnética
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