Encapsulate Bryostatin-1 by targeted exosomes enhances remyelination and neuroprotection effects of cuprizone induced demyelinating animal model of multiple sclerosis

2021 ◽  
Author(s):  
Xiao-Yu Wu ◽  
Baoying Liao ◽  
Dan Xiao ◽  
Wen-Cheng Wu ◽  
Yun Xiao ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Animal Model ◽  
Effective Treatment ◽  
Neurological Disease ◽  
Demyelinating Disease ◽  
Bryostatin 1 ◽  
Treatment Methods ◽  
The Past ◽  
Novel Therapeutic

Demyelinating disease is a critical neurological disease, and there is still a lack of effective treatment methods. In the past two decades, stem cells have emerged as a novel therapeutic...

scholarly journals Unexpected Microglial “De-activation” Associated With Altered Synaptic Transmission in the Early Stages of an Animal Model of Multiple Sclerosis

2019 ◽  
Vol 13 ◽  
pp. 117906951982588 ◽  
Author(s):  
Shaona Acharjee ◽  
Quentin J Pittman
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Basolateral Amygdala ◽  
Demyelinating Disease ◽  
Unexpected Finding ◽  
Autoimmune Encephalomyelitis ◽  
Functional Changes ◽  
Functional Relevance ◽  
Underlying Mechanisms ◽  
Excitatory Drive

Multiple sclerosis, and its animal model—experimental autoimmune encephalomyelitis (EAE), is a demyelinating disease causing motor and sensory dysfunction, as well as behavioral comorbidities. In exploring possible functional changes underlying behavioral comorbidities in EAE, we observed increased excitatory drive onto the major cells of the basolateral amygdala. This was associated with increased numbers of dendritic spines. An unexpected finding was that microglial cells at this time were in a “deactivated” state, and further studies suggested that the microglial deactivation was responsible for the increased excitatory drive. This is the first report of microglial deactivation in an inflammatory disease and raises many questions as to the underlying mechanisms and functional relevance.

Mesenchymal stem cells as a treatment for multiple sclerosis: a focus on experimental animal studies

2020 ◽  
Vol 31 (2) ◽  
pp. 161-179 ◽  
Author(s):  
Ahmed Lotfy ◽  
Nourhan S. Ali ◽  
Mai Abdelgawad ◽  
Mohamed Salama
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Animal Studies ◽  
Culture Medium ◽  
Therapeutic Effects ◽  
Autoimmune Encephalomyelitis ◽  
Main Factors ◽  
Experimental Autoimmune

AbstractMultiple sclerosis (MS) is a progressive and debilitating neurological condition in which the immune system abnormally attacks the myelin sheath insulating the nerves. Mesenchymal stem cells (MSCs) are found in most adult tissues and play a significant systemic role in self-repair. MSCs have promising therapeutic effects in many diseases, such as autoimmune diseases, including MS. MSCs have been tested in MS animal models, such as experimental autoimmune encephalomyelitis. Other studies have combined other agents with MSCs, genetically modified MSCs, or used culture medium from MSCs. In this review, we will summarize these studies and compare the main factors in each study, such as the source of MSCs, the type of animal model, the route of injection, the number of injected cells, and the mechanism of action.

scholarly journals Virus Persistence in an Animal Model of Multiple Sclerosis Requires Virion Attachment to Sialic Acid Coreceptors

2004 ◽  
Vol 78 (16) ◽  
pp. 8860-8867 ◽  
Author(s):  
A. S. Manoj Kumar ◽  
Honey V. Reddi ◽  
Aisha Y. Kung ◽  
Mauro Dal Canto ◽  
Howard L. Lipton
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Sialic Acid ◽  
Demyelinating Disease ◽  
Direct Role ◽  
Virus Persistence ◽  
Sialic Acid Binding ◽  
Relevant Animal Model ◽  
Encephalomyelitis Virus ◽  
The Central Nervous System

ABSTRACT Persistent Theiler's virus infection in the central nervous system (CNS) of mice provides a highly relevant animal model for multiple sclerosis. The low-neurovirulence DA strain uses sialic acid as a coreceptor for cell binding before establishing infection. During adaptation of DA virus to growth in sialic acid-deficient cells, three amino acid substitutions (G1100D, T1081I, and T3182A) in the capsid arose, and the virus no longer used sialic acid as a coreceptor. The adapted virus retained acute CNS virulence, but its persistence in the CNS, white matter inflammation, and demyelination were largely abrogated. Infection of murine macrophage but not oligodendrocyte cultures with the adapted virus was also significantly reduced. Substitution of G1100D in an infectious DA virus cDNA clone demonstrated a major role for this mutation in loss of sialic acid binding and CNS persistence. These data indicate a direct role for sialic acid binding in Theiler's murine encephalomyelitis virus persistence and chronic demyelinating disease.

scholarly journals Scoring disease in an animal model of multiple sclerosis using a novel infrared-based automated activity-monitoring system

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shailesh K. Shahi ◽  
Samantha N. Freedman ◽  
Rachel A. Dahl ◽  
Nitin J. Karandikar ◽  
Ashutosh K. Mangalam
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Disease Severity ◽  
Inverse Correlation ◽  
Therapeutic Agents ◽  
Scoring Methods ◽  
Automated Method ◽  
The Central Nervous System ◽  
Disease Scoring ◽  
Novel Therapeutic

AbstractMultiple sclerosis (MS) is a chronic demyelinating disorder of the central nervous system (CNS). Its corresponding animal model, experimental autoimmune encephalomyelitis (EAE), is widely used to understand disease pathogenesis and test novel therapeutic agents. However, existing methods to score EAE disease severity are subjective and often vary between individual researchers, making it difficult to translate findings across different studies. An enhanced automated method of disease scoring would eliminate subjectivity and reduce operator-dependent errors. Here, we used an Infra-Red Activity Monitoring System (IRAMS) to measure murine locomotor activity as a surrogate measure of disease severity and compared it to standard EAE scoring methods. In mice immunized with CNS-specific myelin antigens, we observed an inverse correlation between disease severity and mouse activity, with the IRAMS showing enhanced disease scoring compared to standard EAE scoring methods. Relative to standard EAE scoring methods, IRAMS showed comparable measurement of disease relapses and remissions in the SJL/J-relapsing-remitting model of EAE, and could comparably assess the therapeutic efficiency of the MS drug, Copaxone (Glatiramer acetate-GA). Thus, the IRAMS is a method to measure disease severity in EAE without subjective bias and is a tool to consistently assess the efficacy of novel therapeutic agents for MS.

Brain-derived neurotrophic factor gene delivery in an animal model of multiple sclerosis using bone marrow stem cells as a vehicle

2009 ◽  
Vol 210 (1-2) ◽  
pp. 40-51 ◽  
Author(s):  
Tapas K. Makar ◽  
Christopher T. Bever ◽  
Ishwar S. Singh ◽  
Walter Royal ◽  
Surasri Nandan Sahu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Bone Marrow ◽  
Animal Model ◽  
Gene Delivery ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Bone Marrow Stem Cells ◽  
Factor Gene

Stem cell therapy in multiple sclerosis: promise and controversy

2008 ◽  
Vol 14 (4) ◽  
pp. 541-546 ◽  
Author(s):  
ID Duncan ◽  
S Goldman ◽  
WB Macklin ◽  
M Rao ◽  
LP Weiner ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Neurological Disease ◽  
Research Priorities ◽  
Current State ◽  
Stem And Progenitor Cells ◽  
National Multiple Sclerosis Society ◽  
Development In Vitro

Stem cells offer the potential for regeneration of lost tissue in neurological disease, including multiple sclerosis (MS). Their development in vitro and their use in vivo in animal models of degenerative neurological disease and recent first efforts in human clinical trials were the topics of a recent international meeting sponsored by the Multiple Sclerosis International Federation and the National Multiple Sclerosis Society on “Stem Cells & MS: Prospects and Strategies” Participants reviewed the current state of knowledge about the potential use of stem and progenitor cells in MS and other degenerative neurological disorders and outlined a series of urgent fundamental and applied clinical research priorities that should allow the potential of regeneration of damaged tissue in MS to be assessed and pursued.

Emerging Therapies for Multiple Sclerosis

2010 ◽  
Vol 12 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Stephanie Syc ◽  
Nicoline Schiess
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Treatment Options ◽  
Dramatic Improvement ◽  
The Past ◽  
Emerging Therapies ◽  
The Us ◽  
The Central Nervous System ◽  
Acute Attacks ◽  
New Treatments

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that can result in severe morbidity and mortality. The past 15 years have seen a dramatic improvement in the available treatment options for MS patients. Before the 1990s, steroids administered during acute attacks were the only effective medications for the disease. Since then, seven drugs have been approved by the US Food and Drug Administration for use in MS, and many trials investigating new treatments are in progress. The experimental agents range from vaccines to monoclonal antibodies to drugs with novel mechanisms of action. In addition, the importance of vitamin D and its interaction with the immune system has become increasingly apparent. This selective review of current clinical trials provides a concise summary of promising new MS therapies on the horizon.

scholarly journals Fluvoxamine stimulates oligodendrogenesis of cultured neural stem cells and attenuates inflammation and demyelination in an animal model of multiple sclerosis

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Majid Ghareghani ◽  
Kazem Zibara ◽  
Heibatollah Sadeghi ◽  
Shima Dokoohaki ◽  
Hossein Sadeghi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Animal Model ◽  
Neural Stem Cells

scholarly journals Multiple Transplantation of Mesenchymal Stem Cells in an Active Progressive Multiple Sclerosis Patient: Long Term Therapeutic Outcomes.

2021 ◽  
Author(s):  
Shijie Liu ◽  
Xihong Mao ◽  
Zongliu Hou ◽  
Huan Wei ◽  
Hui Gao ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Demyelinating Disease ◽  
Progressive Multiple Sclerosis ◽  
Beneficial Effects ◽  
Therapeutic Outcomes ◽  
Potential Alternative ◽  
Edss Score

Abstract Background: Multiple sclerosis (MS) is one of the most common idiopathic inflammatory demyelinating disease. One of the challenges in the treatment of MS is how to overcome relapses without severe adverse effects. Due to their immunoregulatory properties and safety, mesenchymal stem cells (MSCs), present a potential alternative for treatment for MS. Objectives: The efficacy and safety of a long-term MSCs therapy in MS remain to be established. In this communication, we report the clinical condition and disease progression of an MS patient treated for 11 years, with multiple infusions of MSCs derived from either his bone marrow (BM), pooled human umbilical cords (UC), or from his own child umbilical cord. Methods: A male patient diagnosed as progressive MS (EDSS score 3) was enrolled into our study and received 1×106 cells/kg of MSCs, at least once a year for 9 years. Results: The MSCs treatment was well tolerated with no significant side effects. Following the transplantation of MSCs, the overall EDSS scores of the patient decreased over the 10 years period of observation. MRI investigation did not reveal any new lesions. However, upon the cessation of the MSCs treatment, the EDSS score increased from 1.0 to 3.5, further supporting the notion that in such a patient, the transplantation of MSCs, had a significant beneficial effect. Conclusions: This case study is the first to report on the beneficial effects of multiple infusions of BM- and UC-MSCs in a progressive MS patient, over a period of 11 years, in absence of any other treatments. Hence, multiple infusions of MSCs may provide a novel therapeutic avenue for patients with aggressive MS.

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