Dietary factors in experimental autoimmune encephalomyelitis and multiple sclerosis: A comprehensive review

2020 ◽  
pp. 135245852092395
Author(s):  
Claire Valburg ◽  
Anup Sonti ◽  
Joel NH Stern ◽  
Souhel Najjar ◽  
Asaff Harel
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Animal Model ◽  
Randomized Clinical Trials ◽  
Dietary Intervention ◽  
Autoimmune Encephalitis ◽  
Dietary Factors ◽  
Comprehensive Review ◽  
Therapeutic Implications ◽  
Experimental Autoimmune

Background: Dietary intervention in multiple sclerosis carries potential therapeutic implications. While studies utilizing animal models of multiple sclerosis (MS) have demonstrated intriguing findings, well-designed clinical trials are few in number. Objective: The objective of this study is to review the animal model and clinical literature regarding dietary factors in experimental autoimmune encephalitis (EAE) and MS. Methods: This manuscript provides a comprehensive review of current animal model and clinical knowledge related to dietary factors in MS. Results: While there is currently little data for any specific diet in MS, there is growing evidence that certain dietary factors may influence the disease. Conclusions: Definitive information regarding dietary factors as a modifiable risk factor in MS will require larger randomized clinical trials.

scholarly journals CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daekwon Bae ◽  
Ji-Young Lee ◽  
Nina Ha ◽  
Jinsol Park ◽  
Jiyeon Baek ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Autoimmune Encephalitis ◽  
Selective Inhibitor ◽  
Therapeutic Effects ◽  
Treatment Regimens ◽  
Ifn Γ ◽  
Experimental Autoimmune

AbstractDespite advances in therapeutic strategies for multiple sclerosis (MS), the therapy options remain limited with various adverse effects. Here, the therapeutic potential of CKD-506, a novel HDAC6-selective inhibitor, against MS was evaluated in mice with myelin oligodendrocyte glycoprotein35–55 (MOG35–55)-induced experimental autoimmune encephalitis (EAE) under various treatment regimens. CKD-506 exerted prophylactic and therapeutic effects by regulating peripheral immune responses and maintaining blood–brain barrier (BBB) integrity. In MOG35–55-re-stimulated splenocytes, CKD-506 decreased proliferation and downregulated the expression of IFN-γ and IL-17A. CKD-506 downregulated the levels of pro-inflammatory cytokines in the blood of EAE mice. Additionally, CKD-506 decreased the leakage of intravenously administered Evans blue into the spinal cord; CD4+ T cells and CD4−CD11b+CD45+ macrophage/microglia in the spinal cord was also decreased. Moreover, CKD-506 exhibited therapeutic efficacy against MS, even when drug administration was discontinued from day 15 post-EAE induction. Disease exacerbation was not observed when fingolimod was changed to CKD-506 from day 15 post-EAE induction. CKD-506 alleviated depression-like behavior at the pre-symptomatic stage of EAE. In conclusion, CKD-506 exerts therapeutic effects by regulating T cell- and macrophage-mediated peripheral immune responses and strengthening BBB integrity. Our results suggest that CKD-506 is a potential therapeutic agent for MS.

scholarly journals Citicoline in Ophthalmological Neurodegenerative Disease: A Comprehensive Review

2021 ◽  
Vol 14 (3) ◽  
pp. 281
Author(s):  
Francesco Oddone ◽  
Luca Rossetti ◽  
Mariacristina Parravano ◽  
Diego Sbardella ◽  
Massimo Coletta ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Diabetic Retinopathy ◽  
Neurodegenerative Diseases ◽  
Brain Ischemia ◽  
Metabolic Pathways ◽  
Randomized Clinical Trials ◽  
Mitochondrial Dynamics ◽  
Ischemic Optic Neuropathy ◽  
Comprehensive Review ◽  
Dopaminergic Transmission

Cytidine 5’-diphosphocholine has been widely studied in systemic neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, and brain ischemia. The rationale for the use of citicoline in ophthalmological neurodegenerative diseases, including glaucoma, anterior ischemic optic neuropathy, and diabetic retinopathy, is founded on its multifactorial mechanism of action and the involvement in several metabolic pathways, including phospholipid homeostasis, mitochondrial dynamics, as well as cholinergic and dopaminergic transmission, all being involved in the complexity of the visual transmission. This narrative review is aimed at reporting both pre-clinical data regarding the involvement of citicoline in such metabolic pathways (including new insights about its role in the intracellular proteostasis through an interaction with the proteasome) and its effects on clinical psychophysical, electrophysiological, and morphological outcomes following its use in ophthalmological neurodegenerative diseases (including the results of the most recent prospective randomized clinical trials).

AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

2021 ◽  
Author(s):  
William E. Barclay ◽  
M. Elizabeth Deerhake ◽  
Makoto Inoue ◽  
Toshiaki Nonaka ◽  
Kengo Nozaki ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Animal Model ◽  
Cell Death ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammasome Activation ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are such autoimmune conditions influenced by inflammasomes. Despite work investigating inflammasomes during EAE, little remains known concerning the role of inflammasomes in the central nervous system (CNS) during the disease. Here we use multiple genetically modified mouse models to monitor activated inflammasomes in situ based on ASC oligomerization in the spinal cord. Using inflammasome reporter mice, we found heightened inflammasome activation in astrocytes after the disease peak. In contrast, microglia and CNS-infiltrated myeloid cells had few activated inflammasomes in the CNS during EAE. Astrocyte inflammasome activation was dependent on AIM2, but low IL-1β expression and no significant signs of cell death were found in astrocytes during EAE. Thus, the AIM2 inflammasome activation in astrocytes may have a distinct role from traditional inflammasome-mediated inflammation.SIGNIFICANCE STATEMENTInflammasome activation in the peripheral immune system is pathogenic in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, inflammasome activity in the central nervous system (CNS) is largely unexplored. Here, we used genetically modified mice to determine inflammasome activation in the CNS during EAE. Our data indicated heightened AIM2 inflammasome activation in astrocytes after the disease peak. Unexpectedly, neither CNS-infiltrated myeloid cells nor microglia were the primary cells with activated inflammasomes in SC during EAE. Despite AIM2 inflammasome activation, astrocytes did not undergo apparent cell death and produced little of the proinflammatory cytokine, IL-1β, during EAE. This study showed that CNS inflammasome activation occurs during EAE without associating with IL-1β-mediated inflammation.

Multiple sclerosis pathogenesis: missing pieces of an old puzzle

2018 ◽  
Vol 30 (1) ◽  
pp. 67-83 ◽  
Author(s):  
Reza Rahmanzadeh ◽  
Wolfgang Brück ◽  
Alireza Minagar ◽  
Mohammad Ali Sahraian
Keyword(s):  
Multiple Sclerosis ◽  
Cd8 T Cells ◽  
Autoimmune Encephalitis ◽  
Cd4 T Cell ◽  
Experimental Autoimmune Encephalitis ◽  
Focal Lesions ◽  
Multiple Sclerosis Pathogenesis ◽  
Cns Autoimmunity ◽  
Ms Pathogenesis ◽  
Experimental Autoimmune

Abstract Traditionally, multiple sclerosis (MS) was considered to be a CD4 T cell-mediated CNS autoimmunity, compatible with experimental autoimmune encephalitis model, which can be characterized by focal lesions in the white matter. However, studies of recent decades revealed several missing pieces of MS puzzle and showed that MS pathogenesis is more complex than the traditional view and may include the following: a primary degenerative process (e.g. oligodendroglial pathology), generalized abnormality of normal-appearing brain tissue, pronounced gray matter pathology, involvement of innate immunity, and CD8 T cells and B cells. Here, we review these findings and discuss their implications in MS pathogenesis.

scholarly journals Author response: A comprehensive review of randomized clinical trials in three medical journals reveals 396 medical reversals

2019 ◽  
Author(s):  
Diana Herrera-Perez ◽  
Alyson Haslam ◽  
Tyler Crain ◽  
Jennifer Gill ◽  
Catherine Livingston ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Author Response ◽  
Medical Journals ◽  
Comprehensive Review

scholarly journals From Conventional to Precision Therapy in Canine Mammary Cancer: A Comprehensive Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Guillermo Valdivia ◽  
Ángela Alonso-Diez ◽  
Dolores Pérez-Alenza ◽  
Laura Peña
Keyword(s):  
Animal Model ◽  
Targeted Therapies ◽  
Mammary Cancer ◽  
Hormone Receptors ◽  
Randomized Clinical Trials ◽  
Epithelial Mesenchymal Transition ◽  
Comprehensive Review ◽  
Mesenchymal Transition ◽  
Canine Mammary Cancer

Canine mammary tumors (CMTs) are the most common neoplasm in intact female dogs. Canine mammary cancer (CMC) represents 50% of CMTs, and besides surgery, which is the elective treatment, additional targeted and non-targeted therapies could offer benefits in terms of survival to these patients. Also, CMC is considered a good spontaneous intermediate animal model for the research of human breast cancer (HBC), and therefore, the study of new treatments for CMC is a promising field in comparative oncology. Dogs with CMC have a comparable disease, an intact immune system, and a much shorter life span, which allows the achievement of results in a relatively short time. Besides conventional chemotherapy, innovative therapies have a large niche of opportunities. In this article, a comprehensive review of the current research in adjuvant therapies for CMC is conducted to gather available information and evaluate the perspectives. Firstly, updates are provided on the clinical–pathological approach and the use of conventional therapies, to delve later into precision therapies against therapeutic targets such as hormone receptors, tyrosine kinase receptors, p53 tumor suppressor gene, cyclooxygenases, the signaling pathways involved in epithelial–mesenchymal transition, and immunotherapy in different approaches. A comparison of the different investigations on targeted therapies in HBC is also carried out. In the last years, the increasing number of basic research studies of new promising therapeutic agents on CMC cell lines and CMC mouse xenografts is outstanding. As the main conclusion of this review, the lack of effort to bring the in vitro studies into the field of applied clinical research emerges. There is a great need for well-planned large prospective randomized clinical trials in dogs with CMC to obtain valid results for both species, humans and dogs, on the use of new therapies. Following the One Health concept, human and veterinary oncology will have to join forces to take advantage of both the economic and technological resources that are invested in HBC research, together with the innumerable advantages of dogs with CMC as a spontaneous animal model.

Sign in / Sign up

Export Citation Format

Share Document