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Myelin Repair And Neuroprotection In Multiple Sclerosis
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Book Synopsis Myelin Repair and Neuroprotection in Multiple Sclerosis by : Ian D. Duncan
Download or read book Myelin Repair and Neuroprotection in Multiple Sclerosis written by Ian D. Duncan and published by Springer Science & Business Media. This book was released on 2012-08-31 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt: Myelin Repair and Neuroprotection in Multiple Sclerosis presents an up-date on the translational potential of promoting remyelination in multiple sclerosis (MS). A number of research frontiers still exist in this challenging disease. The cause remains elusive, preventing breakthroughs in its prevention. The move towards oral immunomodulatory therapies has been a major advance, as has the finding of new genes linked to susceptibility that may open the door to new therapeutic approaches. However, a frontier that has been making significant strides in recent years has been that surrounding the neurobiology of myelin regeneration and axon protection: such have been the advances that clinical translation is on the cusp of being achieved. Two broad approaches to therapeutic enhancement of remyelination are envisaged: promoting endogenous remyelination by targeting cells present in the CNS, or, replacing lost myelinating cells from exogenous sources. Current research on oligodendrocyte biology, the pathology of MS, imaging of lesions and the biology of remyelination are paving the way toward opening this new translational frontier. Professor Duncan and Professor Franklin have assembled a broad group of experts in the fields of glial cell biology, neuropathology, radiology and clinical neurology to provide the background toward taking remyelination from experimented models into MS patients.
Author :National Institute of Neurological and Communicative Disorders and Stroke. Office of Scientific and Health Reports Publisher : ISBN 13 : Total Pages :20 pages Book Rating :4.:/5 ( download)
Book Synopsis Multiple Sclerosis by : National Institute of Neurological and Communicative Disorders and Stroke. Office of Scientific and Health Reports
Download or read book Multiple Sclerosis written by National Institute of Neurological and Communicative Disorders and Stroke. Office of Scientific and Health Reports and published by . This book was released on 1978 with total page 20 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Verbatim Record of the 1422nd Meeting, Held at Headquarters, New York, on Thursday, 15 July 1993 by :
Download or read book Verbatim Record of the 1422nd Meeting, Held at Headquarters, New York, on Thursday, 15 July 1993 written by and published by . This book was released on 1993 with total page 56 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Multiple Sclerosis 3, Volume 34 E-Book by : Claudia Lucchinetti
Download or read book Multiple Sclerosis 3, Volume 34 E-Book written by Claudia Lucchinetti and published by Elsevier Health Sciences. This book was released on 2009-10-29 with total page 487 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple Sclerosis 3 emphasizes the latest in the pharmacologic treatment of this incurable inflammatory demyelinating disorder. Primary editors Claudia Lucchinetti, MD, and Reinhard Hohlfeld, MD, with the aid of all new contributors, present a complete and current reference on multiple sclerosis that includes discussions of such hot topics as Biomarkers, Genomics, and Surrogate Outcomes in MS; Pediatric MS; Transverse Myelitis; Attack Therapies in MS; Current Disease-Modifying Therapeutic Strategies in MS; Management of Aggressive MS; Symptomatic Therapies in MS; Complementary and Alternative Medical Therapies; and Strategies to Promote Neuroprotection and Repair. Distinguish between MS and other similar demyelinating disorders and know the best and most aggressive methods of treatment. This title in the Blue Books of Neurology series is exactly what you need to treat the disease and its relapses. Covers the latest clinical advances and relevant discussions—Biomarkers, Genomics, and Surrogate Outcomes in MS; Pediatric MS; Transverse Myelitis; Attack Therapies in MS; Current Disease-Modifying Therapeutic Strategies in MS; Management of Aggressive MS; Symptomatic Therapies in MS; Complementary and Alternative Medical Therapies; and Strategies to Promote Neuroprotection and Repair—to bring you up to date and keep your practice state-of-the-art. Features a greater emphasis on practical management to help you determine the type of multiple sclerosis and the best course of therapy. Focuses on pharmaceutical therapies so you know the best and most aggressive methods and which drugs to use for treatment. Includes extensive information on differential diagnosis so that you can clearly distinguish between multiple sclerosis and other similar demyelinating disorders. Presents expert new editors and experienced contributing authors for the most current and relevant practice information. Emphasizes the pharmacologic management of patients with multiple sclerosis to address treating the actual disease and its relapses as well as treating the symptoms.
Book Synopsis Multiple Sclerosis by : Michael Olek
Download or read book Multiple Sclerosis written by Michael Olek and published by Springer Science & Business Media. This book was released on 2007-10-27 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: A synthesis of current concepts about the evaluation, treatment, and future directions in MS. On the evaluation side, the authors review the use of MRI, magnetic resonance spectroscopy, functional MRI, and three-dimensional MRI, and consider the rapidly developing body of pathologic information they have yielded. On the treatment side, the focus is on recently approved medications (Novantrone), new indications for medications (CHAMPS Trial), medications in development (Oral Interferon Tau, Oral Copaxone, and Oral Cellcept), immunosuppressive therapy for both progressive disease and symptomatic therapy; the current medications for treating relapsing-remitting MS (Avonex, Betaseron, and Copaxone) are also discussed. For future directions, the authors present the current best thinking, as well as the latest discoveries in immunology relating to MS, including groundbreaking B-cell research and its applications to specific immunotherapies, and the use of immune markers for tracking the disease.
Book Synopsis Exploring Molecular and Cellular Strategies for Neuroprotection and Neuroregeneration in Multiple Sclerosis by : Martin Short
Download or read book Exploring Molecular and Cellular Strategies for Neuroprotection and Neuroregeneration in Multiple Sclerosis written by Martin Short and published by . This book was released on 2015 with total page 570 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple Sclerosis (MS) is an incurable neurological condition that affects close to 1 in 1000 Australians. Research into the complex aetiology and pathophysiology of MS is rapidly advancing. Many new treatments targeting the immune system are now available and can partially prevent damage caused by inflammation. However, all patients have a degree of axonal loss and neurodegeneration that can contribute to long-term disability. So far, no treatment has demonstrated an ability to directly protect the central nervous system (CNS) of MS patients from axonal injury or neurodegeneration. No treatment has shown to remyelinate or regenerate injured tissue in clinical trials. There is therefore a great demand for a therapy that can not only modulate the immune system but also protect the brain from axonal injury and facilitate repair processes. The aim of this thesis was to explore potential therapeutic approaches to neuroprotection and neuroregeneration in Multiple Sclerosis. Direct cell replacement was assessed using bone marrow derived cells in an animal model of Multiple Sclerosis, experimental autoimmune encephalomyelitis (EAE). The ability of mesenchymal stem cells (MSCs) and amnion epithelial cells (AECs) to protect human neural stem cells from oxidative stress injury and to differentiate through the production of neurotrophic factors was examined in vitro. Finally, several cytoskeletal proteins important for axonal growth were characterised. Their relationship with the Nogo receptor and changes due to inflammation from EAE were investigated.The ability of bone marrow derived cells to directly replace and regenerate cells within the uninjured or inflamed brain and spinal cord was assessed in the first part of the thesis. Despite the use of a highly sensitive multi-colour flow cytometry, an insignificant number of the bone marrow derived cells transplanted into mice were able to transform into neural cells. These findings were confirmed using immunofluorescence microscopy and virtual slide imaging. Although more bone marrow derived cells migrated to the brain and spinal cord in mice with EAE than controls, they retained hematopoietic cell markers, hence confirming the lack of transformation.While bone marrow predominantly contains hematopoietic cells and their precursors, there are other cell types including MSCs that have been investigated as a possible novel therapy for Multiple Sclerosis. As well as modulating the immune system, these cells have potential for neuroprotection and regeneration. Rather than direct cell replacement, these cells possibly have their effect through the production of soluble factors. We have demonstrated that MSC express RNA for many neurotrophic factors and in particular produce IL-6, BDNF and HGF. The quantity of these factors was increased following exposure to pro-inflammatory cytokines, particularly TNF-[alpha]. In the second part of the thesis, a novel culture system in which neural stem cells (NSCs) derived from a patient with MS using induced pluripotent stem cell techniques was used to assess the ability of human MSC to protect against oxidative stress and enhance differentiation through the production of neurotrophic factors. NSCs exposed to MSC conditioned media for 5 weeks reduced the expression of GFAP expression and a low molecular weight component within the conditioned media ameliorated oxidative stress.Although bone marrow derived MSC have many attractive attributes for use as an immunomodulatory and neuroregenerative therapy in MS, the need for cell culture and expansion may limit its use. AECs are an alternative cell type obtained in large numbers from otherwise discarded placentas that has promise for use in inflammatory conditions including MS. The neuroprotective and regenerative potential in MS has not previously been examined. The ability of AECs to produce neurotrophic factors was investigated and compared with MSCs. AECs expressed fewer neurotrophic factors and did not produce IL-6, BDNF or HGF. AEC conditioned media still reduced GFAP expression in NSCs over 5 weeks of culture but appeared to increase oxidative stress and cell death. Similar to MSCs, the AEC conditioned media appeared to ameliorate the effect of an exogenous oxidative stress.While cell therapies have great potential in regenerative medicine, there are a number of other promising avenues of research. In the final part of the thesis, possible mechanisms underlying Nogo receptor mediated restriction in axonal growth have been explored. Two proteins downstream of the Nogo Receptor, CRMP-2 and cofilin were examined. Phosphorylated CRMP-2 correlated well with axonal loss in both the animal model of MS (EAE) and biopsy sections from an MS patient. Levels of phosphorylated cofilin were higher in mice lacking the Nogo receptor than the controls. Since cofilin phosphorylation is linked to axonal growth, if substantiated, these findings could potentially lead to novel and targeted therapies for regeneration in MS.This thesis has explored a range of different strategies that show promise for neuroprotection and regeneration in MS from direct cell replacement by bone marrow stem cells, the production of neurotrophic factors by MSCs and AECs, and modulation of the Nogo receptor via CRMP-2 and cofilin. Due to the great demand for neuroprotective and regenerative therapies these and other therapies are already being translated into early clinical trials. Although current immunomodulatory therapies can significantly reduce relapses and lesion load over time, a combination of immunomodulatory and neuroprotective/regenerative therapies may have a greater impact on reducing long-term disability and improve the quality of life for patients with MS.
Book Synopsis Multiple Sclerosis As A Neuronal Disease by : Stephen Waxman
Download or read book Multiple Sclerosis As A Neuronal Disease written by Stephen Waxman and published by Elsevier. This book was released on 2005-05-27 with total page 495 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book examines the role of neurons in multiple sclerosis (MS) and the changes that occur in neurons as a result of MS. It places MS in a new and important perspective that not only explains the basis for symptom production, remission, and progress in MS, but also promises to open up new therapeutic possibilities.* Brings together the latest information from clinical, pathological, imaging, molecular, and pharmacological realms to explore the neurobiology of Multiple Sclerosis* Places MS in a new and important perspective that promises to open up new therapeutic avenues* Superbly illustrated and referenced
Book Synopsis Mechanisms of Neuroprotection and Remyelination in Demyelinating Disease Models of Multiple Sclerosis: A Lesson From Estrogen Receptor Specific Ligands by : Youn-Jung Roy Kim
Download or read book Mechanisms of Neuroprotection and Remyelination in Demyelinating Disease Models of Multiple Sclerosis: A Lesson From Estrogen Receptor Specific Ligands written by Youn-Jung Roy Kim and published by . This book was released on 2018 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt: Currently, available drugs for multiple sclerosis (MS) are predominantly immune-modulatory. They are effective in reducing relapses, but not in slowing down or stopping progressive disease course. Therefore, there is a need to develop treatment strategies that will provide neuroprotection and halt disability progression. Pregnancy is neuroprotective in patients with MS. A pregnancy hormone and a moderate estrogen receptor beta (ER )-ligand, estriol, has been reported to have beneficial effects on reducing relapses and improving cognition when treated in MS patients. Although, the mechanisms of ER -ligand mediated treatment effects on neuroprotection remains poorly understood. Here I hypothesized that ER signaling on CD11c+ immune cells and Olig1+ oligodendrocytes plays an essential role in providing neuroprotection and enhancing remyelination. To test the hypothesis, I created conditional knockout mice (CKO) with ER deleted from each cell type using the Cre-LoxP recombinase system and investigated neuroprotective effects of ER -ligand treatment in experimental autoimmune encephalomyelitis (EAE) and cuprizone diet-induced demyelinating disease models. Also, I used RiboTag mice to determine oligodendrocyte specific gene expression to understand the molecular mechanisms of remyelination. Subsequently, I studied the mechanisms of ER -ligand treatment effects in oligodendrocytes during remyelination. The results revealed that ER -ligand treatment reduced pro-inflammatory responses through ER on CD11c+ myeloid DC/M and increased oligodendrocyte maturation through ER on Olig1+ oligodendrocytes during EAE. The use of CKO mice proved that both were necessary as one without the other was not sufficient. Mechanistic insights on remyelination using the RiboTag mice revealed that oligodendrocytes upregulate de novo cholesterol biosynthesis during remyelination after chronic demyelination. Furthermore, when compared to vehicle treated naturally remyelinating mice, ER -ligand treated mice showed enhanced remyelination by increasing oligodendrocyte maturation, increasing cholesterol synthesis pathway genes, increasing oligodendrocyte progenitor cells (OPCs), and increasing Sox2 expression in OPCs during remyelination. I extended our investigation of ER -ligand treatment in the cuprizone model to the EAE model, to discover that ER -ligand treated mice showed neuroprotection by increasing oligodendrocyte maturation, and increasing cholesterol synthesis pathway genes, but not by increasing OPC Sox2 expression. This comprehensive approach using two different demyelinating disease models of MS and two transgenic mouse models provided critical insights regarding treatment effects of ER -ligand on neuroprotection and remyelination in vivo.
Book Synopsis Myelination and Demyelination by : Seung U. Kim
Download or read book Myelination and Demyelination written by Seung U. Kim and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 276 pages. Available in PDF, EPUB and Kindle. Book excerpt: In June 1987, neurobiologists, immunologists, molecular biologists, virologists and neurologists from several countries met in Vancouver to discuss recent advances of relevance to multiple sclerosis. The symposium was a part of the 22nd Canadian Congress of Neurological Sciences meeting and was sponsored by funds from the Multiple Sclerosis Society of Canada and the Medical Research Council of Canada. The presentations covered five major topics: basic neurobiology, molecular biology, the role of viruses in demyelination, immune function and dysfunction in multiple sclerosis, and clinical magnetic resonance imaging studies. It was heartening to note that scientists from several different disciplines were working towards a common end-point: the understanding and treatment of multiple sclerosis. In this book, speakers at the symposium have each presented a chapter of their findings and discussions. In addition, some non-participants at the symposium have been invited to submit chapters in order to give this volume a more complete scope. It is hoped that the reader will find this book a useful reference for several subjects of interest to multiple sclerosis. In closing, I would like to thank the following for their help and support: the Multiple Sclerosis Society of Canada and the Medical Research Council of Canada for their financial support; the contributors of this book for their manuscripts; Dr. A. Eisen, Mrs. K. Eisen, Mrs. P. Bodnarchuk and Mrs. M. Kim for their efforts in planning and organizing the symposium; and Ms. Catherine Schikowski for her secretarial assistance. Seung U. Kim, M.D. Ph.D.
Book Synopsis Neuroimmune Diseases by : Hiroshi Mitoma
Download or read book Neuroimmune Diseases written by Hiroshi Mitoma and published by Springer. This book was released on 2019-08-13 with total page 822 pages. Available in PDF, EPUB and Kindle. Book excerpt: A translational overview of neuroimmune diseases for neuroscientists and clinicians that clarifies the pathological mechanisms underlying neuroimmune diseases and builds a comprehensive bridge between the latest research findings and their clinical implications in daily practice. The material is presented in two steps. The first section comprises a review of the pathogenic actions of immune cells in brain diseases. Here the authors discuss the mechanisms through which immune cells disrupt the functions of nerve cells. The second section explores the ways in which the brain becomes dysfunctional due to impaired nerve cell function. Based on pathogenesis, diagnostic and therapeutic strategies are discussed for each clinical category. The book will be invaluable for use in clinical practice of neuroimmune diseases
Book Synopsis Neurodegeneration and Neuroprotection in Multiple Sclerosis by : Aaron E. Miller
Download or read book Neurodegeneration and Neuroprotection in Multiple Sclerosis written by Aaron E. Miller and published by . This book was released on 2005 with total page 25 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Multiple Sclerosis by : Institute of Medicine
Download or read book Multiple Sclerosis written by Institute of Medicine and published by National Academies Press. This book was released on 2001-08-10 with total page 457 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is a chronic and often disabling disease of the nervous system, affecting about 1 million people worldwide. Even though it has been known for over a hundred years, no cause or cure has yet been discovered-but now there is hope. New therapies have been shown to slow the disease progress in some patients, and the pace of discoveries about the cellular machinery of the brain and spinal cord has accelerated. This book presents a comprehensive overview of multiple sclerosis today, as researchers seek to understand its processes, develop therapies that will slow or halt the disease and perhaps repair damage, offer relief for specific symptoms, and improve the abilities of MS patients to function in their daily lives. The panel reviews existing knowledge and identifies key research questions, focusing on: Research strategies that have the greatest potential to understand the biological mechanisms of recovery and to translate findings into specific strategies for therapy. How people adapt to MS and the research needed to improve the lives of people with MS. Management of disease symptoms (cognitive impairment, depression, spasticity, vision problems, and others). The committee also discusses ways to build and financially support the MS research enterprise, including a look at challenges inherent in designing clinical trials. This book will be important to MS researchers, research funders, health care advocates for MS research and treatment, and interested patients and their families.
Book Synopsis Neuroprotection and Recovery in Multiple Sclerosis by : Dafin F. Muresanu
Download or read book Neuroprotection and Recovery in Multiple Sclerosis written by Dafin F. Muresanu and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is a complex and heterogeneous immune-mediated disease that results in the progressive accumulation of mental and physical symptoms. Currently approved disease-modifying drugs (DMDs) are immunomodulatory or immunosuppressive, but these drugs have little effect on disease progression. In addition to studies that have directly targeted inflammation and immune responses, a large number of studies, most of them experimental, have investigated neuroprotective therapies and remyelination strategies. However, to date, attempts to provide neuroprotection have failed not just in multiple sclerosis but in neurological disorders in general; this situation has emphasized the need to revise the old paradigm of a "magic bullet" with a single mechanism of action. Remyelination strategies involve either promoting endogenous remyelination or replacing lost myelinating cells through exogenous sources. However, several puzzle pieces regarding the physiology of remyelination remain unknown, including feasible treatment monitoring methods, the selection of patients, and the optimal time of treatment initiation. This chapter will describe the direct and indirect neuroprotective effects of DMDs, as suggested by basic research studies and confirmed by clinical studies in some cases. Current knowledge of potential neuroprotective therapies and remyelination strategies is also reviewed.
Book Synopsis Neuroprotection in multiple sclerosis by : Reinhard Hohlfeld
Download or read book Neuroprotection in multiple sclerosis written by Reinhard Hohlfeld and published by . This book was released on 2004 with total page 54 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Biological Mechanisms Driving Neurodegeneration in Multiple Sclerosis by : Emilie Poirion
Download or read book Biological Mechanisms Driving Neurodegeneration in Multiple Sclerosis written by Emilie Poirion and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple Sclerosis (MS), an inflammatory and demyelinating disease of the central nervous system, is the leading cause of non-traumatic neurological disability in young adults in western countries. It is now well accepted that neurodegeneration is the key mechanism underlying disability progression in this disease. The biological mechanisms leading to neurodegeneration remains poorly understood in vivo, but pathological post-mortem studies have pointed the potential contribution of a persisting inflammation involving the innate immune system together with a failure of endogenous repair in white matter (WM) and cortical lesions. This thesis aimed at developing imaging tools able to quantify and map innate immune cell activation and myelin dynamics though a combination of positron emission tomography (PET) and advanced high field magnetic resonance imaging (MRI) in patients with MS. For this purpose I have first developed a post processing methodology that allows the generation of individual and regional maps of tissue damage and repair, which was used for the quantification of innate immune cell activation as well as for the investigation of demyelination/remyelination in WM lesions and in the cortex. We have combined TSPO PET with [18F]-DPA714, targeting mainly activated innate immune cells, and multimodal 3T MRI, assessing structural damage, in a cohort of MS patients with either a relapsing or a progressive form of the disease. I showed that patients with MS were characterized by a very heterogeneous level of neuroinflammation, and that a large subset of WM lesions considered as inactive on MRI were actually very active on PET, a finding suggestive of chronic active lesions. I further showed that this persisting inflammation correlated with individual trajectories of disability. Then, I have questioned whether the proximity to the cerebrospinal fluid (CSF) could influence innate immune cells in the deep white and grey matter. I demonstrated a clear gradient of innate immune cells activation in vicinity to ventricular CSF, which correlated with the periventricular gradient of microstructural damage, and could also explain part of clinical disability. Aiming to quantify myelin dynamics in the cortex I have applied Magnetization Transfer Imaging and generated individual maps of demyelination and remyelination in cortical tissues. I then showed that cortical and WM individual remyelination profiles were heterogeneous among subjects, and were synergistically contributing to disability in MS. Finally, I have applied for the first time the parallel transmission using dynamic RF-shimming on a 7T MRI system to visualize cortical lesions at the whole brain level, paving the way for an improved detection of these lesions in future studies. Results acquired in this work should allow to apply new imaging tools mapping the mechanisms that drive neurodegeneration in MS in future studies, opening the perspective of patient stratification, novel design for repair and neuroprotection trials, and optimization of care.
Book Synopsis McAlpine's Multiple Sclerosis by : Alastair Compston
Download or read book McAlpine's Multiple Sclerosis written by Alastair Compston and published by . This book was released on 1998 with total page 620 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is the latest edition of the classic book on the subject of multiple sclerosis. An international group of authors has been involved in updating this edition which features more information on imaging and investigations, and a new chapter on neurobiology and glial development.
Book Synopsis Neurodegeneration in Multiple Sclerosis by : M. Filippi
Download or read book Neurodegeneration in Multiple Sclerosis written by M. Filippi and published by Springer Science & Business Media. This book was released on 2008-02-01 with total page 233 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by world-renowned scientists, the volume provides a state-of-the-art on the most recent MRI techniques related to MS, and it is an indispensable tool for all those working in this field. The context in which this book exists is that there is an increasing perception that modern MR methodologies should be more extensively employed in clinical trials to derive innovative information.
