Glial Precursor Cells in the Adult Human Brain

1998 ◽  
Vol 4 (4) ◽  
pp. 264-272 ◽  
Author(s):  
Neil Scolding
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Data ◽  
Demyelinating Diseases ◽  
Culture Techniques ◽  
Myelin Sheaths ◽  
The Central Nervous System ◽  
Glial Precursor ◽  
Tissue Culture Techniques

Oligodendrocytes, the glial cells responsible for laying down and maintaining myelin sheaths in the central nervous system, were first described only 75 years ago. The lineage of these cells, and its relationship with that of the second type of macroglia, the astrocyte, was much studied in vivo and in situ in the rodent over the next 60 years. In the early 1980s, progress in oligodendrocyte biology was markedly amplified by the application of tissue culture techniques–-not without some element of controversy, although this is now largely resolved. Oligodendrocytes have always been given more attention than many other cells as a consequence of their role as a key target in human demyelinating diseases; in fact, few studies of rodent oligodendrocytes fail to draw conclusions regarding multiple sclerosis. Now, however, techniques for studying human glia and their lineage more directly have emerged, and differences in rodent and human oligodendrocyte biology are becoming apparent. It is increasingly clear that some caution must accompany the uncritical extrapolation of rodent experimental data to human oligodendrocyte biology and, indeed, to human disease.

scholarly journals New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination

2020 ◽  
Author(s):  
Sarah A Neely ◽  
Jill M Williamson ◽  
Anna Klingseisen ◽  
Lida Zoupi ◽  
Jason J Early ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Cell ◽  
Live Imaging ◽  
Therapeutic Strategies ◽  
Demyelinating Diseases ◽  
Neuronal Cell Bodies ◽  
The Central Nervous System

Regeneration of myelin (remyelination) in the central nervous system (CNS) has long been thought to be principally mediated by newly generated oligodendrocytes, a premise underpinning therapeutic strategies for demyelinating diseases, including multiple sclerosis (MS). Recent studies have indicated that oligodendrocytes that survive demyelination can also contribute to remyelination, including in MS, but it is unclear how remyelination by surviving oligodendrocytes compares to that of newly generated oligodendrocytes. Here we studied oligodendrocytes in MS, and also imaged remyelination in vivo by surviving and new oligodendrocytes using zebrafish. We define a previously unappreciated pathology in MS, myelination of neuronal cell bodies, which is recapitulated during remyelination by surviving oligodendrocytes in zebrafish. Live imaging also revealed that surviving oligodendrocytes make very few new sheaths, but can support sheath growth along axons. In comparison, newly made oligodendrocytes make abundant new sheaths, properly targeted to axons, and exhibit a much greater capacity for regeneration.

scholarly journals Ultra-high-field 7-T MRI in multiple sclerosis and other demyelinating diseases: from pathology to clinical practice

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Nicolo’ Bruschi ◽  
Giacomo Boffa ◽  
Matilde Inglese
Keyword(s):  
Multiple Sclerosis ◽  
High Field ◽  
Neurological Diseases ◽  
Lesion Detection ◽  
Demyelinating Diseases ◽  
Metabolic Imaging ◽  
Central Vein ◽  
Ultra High Field ◽  
Functional Features

Abstract Magnetic resonance imaging (MRI) is essential for the early diagnosis of multiple sclerosis (MS), for investigating the disease pathophysiology, and for discriminating MS from other neurological diseases. Ultra-high-field strength (7-T) MRI provides a new tool for studying MS and other demyelinating diseases both in research and in clinical settings. We present an overview of 7-T MRI application in MS focusing on increased sensitivity and specificity for lesion detection and characterisation in the brain and spinal cord, central vein sign identification, and leptomeningeal enhancement detection. We also discuss the role of 7-T MRI in improving our understanding of MS pathophysiology with the aid of metabolic imaging. In addition, we present 7-T MRI applications in other demyelinating diseases. 7-T MRI allows better detection of the anatomical, pathological, and functional features of MS, thus improving our understanding of MS pathology in vivo. 7-T MRI also represents a potential tool for earlier and more accurate diagnosis.

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 Ozone therapy in ethidium bromide-induced demyelination in rats: possible protective effect [abstract]

2019 ◽  
Vol 3 (4) ◽  
Author(s):  
Mohga Samy
Keyword(s):  
Multiple Sclerosis ◽  
Protective Effect ◽  
Ethidium Bromide ◽  
Demyelinating Diseases ◽  
Immune Reactivity ◽  
Methyl Prednisolone ◽  
The Central Nervous System ◽  
Group 5 ◽  
Group 2 ◽  
Oxygen Groups

BACKGROUND: Multiple sclerosis is an autoimmune inflammatory disease of the central nervous system and it is characterized by excessive demyelination PURPOSE: The study aim to investigate the possible protective effect of ozone (O3) in ethidium bromide (EB) induced demyelination in rats either alone or in combination with corticosteroid in order to decreases the dose of steroid therapy. MATERIAL and METHODS: Rats were divided into 7 groups Group (1) normal control rats received saline. Group (2) sham-operated rats received saline. Group (3) sham operated rats received oxygen. Group (4) EB-treated rats received EB. Group (5) EB treated rats received oxygen. Group (6) EB treated rats received methyl prednisolone (MP) Group (7) EB treated rats received half the dose of MP concomitant with ozone. RESULTS: Significant improvement in the brain serotonin, dopamine, noradrenalin. A reduction of MDA,TNF-COX2 immune-reactivity was noticed in MP and oxygen groups . Furthermore, best amelioration was achieved by combining half the dose of methyl-prednisolone with ozone. CONCLUSION: We concluded that ozone has a protective effect on demyelination and can be used due to its protective effect in demyelinating diseases such as multiple sclerosis.

Demyelinating disorders of the central nervous system

2010 ◽  
pp. 4948-4963
Author(s):  
Siddharthan Chandran ◽  
Alastair Compston
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Acute Disseminated Encephalomyelitis ◽  
Demyelinating Diseases ◽  
Demyelinating Disorder ◽  
System P ◽  
The Central Nervous System ◽  
Demyelinating Disorders ◽  
Brain And Spinal Cord

Clinicians suspect demyelination when episodes reflecting damage to white matter tracts within the central nervous system occur in young adults. The paucity of specific biological markers of discrete demyelinating syndromes places an emphasis on clinical phenotype—temporal and spatial patterns—when classifying demyelinating disorders. The diagnosis of multiple sclerosis, the most common demyelinating disorder, becomes probable when these symptoms and signs recur, involving different parts of the brain and spinal cord. Other important demyelinating diseases include post-infectious neurological disorders (acute disseminated encephalomyelitis), demyelination resulting from metabolic derangements (central pontine myelinosis), and inherited leucodystrophies that may present in children or in adults. Accepting differences in mechanism, presentation, and treatment, two observations can usefully be made when classifying demyelinating disorders. These are the presence or absence of inflammation, and the extent of focal vs. diffuse demyelination. Multiple sclerosis is prototypic for the former, whereas dysmyelinating disorders, such as leucodystrophies are representative of the latter....

Neural regulation of lysozyme secretion from tracheal submucosal glands of ferrets in vivo

1991 ◽  
Vol 71 (3) ◽  
pp. 939-944 ◽  
Author(s):  
B. Davis ◽  
H. C. Tseng
Keyword(s):  
Substance P ◽  
Peripheral Nerves ◽  
Specific Marker ◽  
Cell Secretion ◽  
P Content ◽  
Submucosal Glands ◽  
Serous Cell ◽  
The Central Nervous System

To investigate how central and peripheral nerves affect lysozyme secretion from tracheal submucosal glands in ferrets we injected substance P (20 nmol/kg in 200 microliters) intracisternally or intravenously into anesthetized artificially ventilated ferrets. We collected 3-ml samples from a perfused (3 ml/5 min) segment of trachea in situ during 15 min before and 45 min after injection of substance P. Content of lysozyme, a specific marker of tracheal submucosal gland serous cell secretion in ferrets, was measured spectrophotometrically in each sample. Intracisternal substance P increased peak lysozyme output threefold compared with baseline. This increase was abolished completely by cutting both superior laryngeal nerves (SLN) and was partially inhibited by atropine, phentolamine, or propranolol. Intravenous substance P increased peak lysozyme output 10-fold compared with baseline. This increase was partly abolished by cutting both SLN. We concluded that intracisternal substance P stimulated the central nervous system (CNS) and activated cholinergic, adrenergic, and nonadrenergic noncholinergic secretomotor nerves to tracheal glands and that intravenous substance P increased lysozyme secretion both by acting directly on tracheal glands and indirectly on the CNS to activate secretomotor nerves.

scholarly journals Current Methods of Magnetic Resonance for Noninvasive Assessment of Molecular Aspects of Pathoetiology in Multiple Sclerosis

2020 ◽  
Vol 21 (17) ◽  
pp. 6117
Author(s):  
Petra Hnilicová ◽  
Oliver Štrbák ◽  
Martin Kolisek ◽  
Egon Kurča ◽  
Kamil Zeleňák ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Neuronal Degeneration ◽  
Metabolic Stress ◽  
Pathological Process ◽  
Diagnostic Tools ◽  
Powerful Analytical Tool ◽  
The Central Nervous System ◽  
Molecular Aspects

Multiple sclerosis (MS) is an autoimmune disease with expanding axonal and neuronal degeneration in the central nervous system leading to motoric dysfunctions, psychical disability, and cognitive impairment during MS progression. The exact cascade of pathological processes (inflammation, demyelination, excitotoxicity, diffuse neuro-axonal degeneration, oxidative and metabolic stress, etc.) causing MS onset is still not fully understood, although several accompanying biomarkers are particularly suitable for the detection of early subclinical changes. Magnetic resonance (MR) methods are generally considered to be the most sensitive diagnostic tools. Their advantages include their noninvasive nature and their ability to image tissue in vivo. In particular, MR spectroscopy (proton 1H and phosphorus 31P MRS) is a powerful analytical tool for the detection and analysis of biomedically relevant metabolites, amino acids, and bioelements, and thus for providing information about neuro-axonal degradation, demyelination, reactive gliosis, mitochondrial and neurotransmitter failure, cellular energetic and membrane alternation, and the imbalance of magnesium homeostasis in specific tissues. Furthermore, the MR relaxometry-based detection of accumulated biogenic iron in the brain tissue is useful in disease evaluation. The early description and understanding of the developing pathological process might be critical for establishing clinically effective MS-modifying therapies.

scholarly journals Differential diagnosis of suspected multiple sclerosis: a consensus approach

2008 ◽  
Vol 14 (9) ◽  
pp. 1157-1174 ◽  
Author(s):  
DH Miller ◽  
BG Weinshenker ◽  
M Filippi ◽  
BL Banwell ◽  
JA Cohen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Differential Diagnosis ◽  
Evidence Base ◽  
Demyelinating Diseases ◽  
Future Research ◽  
International Panel ◽  
The Central Nervous System ◽  
Definition Of ◽  
Demyelinating Disorders ◽  
Diagnosis Criteria

Background and objectives Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. Methods Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. Results We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of “clinically isolated syndromes” (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. Conclusions Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision.

scholarly journals Plasma complement biomarkers distinguish multiple sclerosis and neuromyelitis optica spectrum disorder

2016 ◽  
Vol 23 (7) ◽  
pp. 946-955 ◽  
Author(s):  
Svetlana Hakobyan ◽  
Sebastian Luppe ◽  
David RS Evans ◽  
Katharine Harding ◽  
Samantha Loveless ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Unmet Need ◽  
Area Under The Curve ◽  
Spectrum Disorder ◽  
Demyelinating Diseases ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Complement Proteins ◽  
Activation Products ◽  
The Central Nervous System

Background: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune inflammatory demyelinating diseases of the central nervous system. Although distinguished by clinicoradiological and demographic features, early manifestations can be similar complicating management. Antibodies against aquaporin-4 support the diagnosis of NMOSD but are negative in some patients. Therefore, there is unmet need for biomarkers that enable early diagnosis and disease-specific intervention. Objective: We investigated whether plasma complement proteins are altered in MS and NMOSD and provide biomarkers that distinguish these diseases. Methods: Plasma from 54 NMOSD, 40 MS and 69 control donors was tested in multiplex assays measuring complement activation products and proteins. Using logistic regression, we tested whether combinations of complement analytes distinguished NMOSD from controls and MS. Results: All activation products were elevated in NMOSD compared to either control or MS. Four complement proteins (C1inh, C1s, C5 and FH) were higher in NMOSD compared to MS or controls. A model comprising C1inh and terminal complement complex (TCC) distinguished NMOSD from MS (area under the curve (AUC): 0.98), while C1inh and C5 distinguished NMOSD from controls (AUC: 0.94). Conclusion: NMOSD is distinguished from MS by plasma complement biomarkers. Selected complement analytes enable differential diagnosis. Findings support trials of anti-complement therapies in NMOSD.

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