Search results for "Myelitis"
showing 10 items of 211 documents
IL-17 and related cytokines involved in the pathology and immunotherapy of multiple sclerosis: Current and future developments.
2014
Multiple sclerosis (MS), an autoimmune neurological disorder, is driven by self-reactive T helper (Th) cells. Research on the role of Th17 lymphocytes in MS pathogenesis has made significant progress in identifying various immunological as well as environmental factors that induce the differentiation and expansion of these cells, different subsets of Th17 cells with varying degrees of pathogenicity, and the role of the secreted effector cytokines. While approved therapies for MS offer significant benefit to patients, there remain unmet needs. Ongoing clinical trials aim to translate the advanced knowledge of Th17 cytokines to improved therapies. This review discusses the current status and …
Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma.
2021
Getting around the blood–brain barrier The meninges comprise three membranes that surround and protect the central nervous system (CNS). Recent studies have noted the existence of myeloid cells resident there, but little is known about their ontogeny and function, and whether other meningeal immune cell populations have important roles remains unclear (see the Perspective by Nguyen and Kubes). Cugurra et al. found in mice that a large proportion of continuously replenished myeloid cells in the dura mater are not blood derived, but rather transit from cranial bone marrow through specialized channels. In models of CNS injury and neuroinflammation, the authors demonstrated that these myeloid c…
Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient KitW-sh/W-sh mice
2011
Mast cell (MC)-deficient c-Kit mutant Kit(W/W-v) mice are protected against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, suggesting a detrimental role for MCs in this disease. To further investigate the role of MCs in EAE, we took advantage of a recently characterized model of MC deficiency, Kit(W-sh/W-sh). Surprisingly, we observed that myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE was exacerbated in Kit(W-sh/W-sh) compared with Kit(+/+) mice. Kit(W-sh/W-sh) mice showed more inflammatory foci in the central nervous system (CNS) and increased T-cell response against myelin. To understand whether the discrepant results obtaine…
Glutamate Excitotoxicity in the Cerebellum Mediated by IL-1β
2013
Multiple sclerosis (MS) is the prototypic inflammatory demyelinating disorder of the CNS. Symptoms of cerebellar dysfunction, such as tremors and ataxia, are relatively common in MS, but available treatment options are generally of limited value. Although many clinical manifestations of MS are
Elevated NKG2D ligand expression in experimental autoimmune encephalomyelitis
2014
T cells remain unclear. Expressing myelin-reactive T cell receptor (TCR) is not sufficient to make a T cell encephalitogenic. In fact, the frequencies of myelin-reactive T cells are comparable between MS patients and healthy individuals, but the ones in MS patients have activated/memory phenotypes. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), myelin-specific T cells activated with antigen presenting cells (APCs) plus myelin peptide are encephalitogenic, whereas T cells activated with anti-CD3/CD28 antibodies are not. This suggests that APCs provide critical cytokines beyond T cell receptor activation and co-stimulation, contributing to encephalitogenicity. To …
The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis.
2019
Th17 cells, known as a highly pro-inflammatory subtype of Th cells, are involved very early in numerous aspects of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) neuropathology. A crucial event for the formation and accumulation of MS lesions is represented by the disruption of the blood brain barrier (BBB) in relapsing-remitting MS. Th17 cells also contribute to the progression of MS/EAE. These events will allow for the passage of inflammatory cells into the brain. Secondary to this, increased recruitment of neutrophils occurs, followed by increased protease activity that will continue to attract macrophages and monocytes, leading to brain inflammation with sus…
Re-Emerging Vaccine-Preventable Diseases in War-Affected Peoples of the Eastern Mediterranean Region—An Update
2017
For the past few decades, the Eastern Mediterranean Region has been one area of the world profoundly shaped by war and political instability. On-going conflict and destruction have left the region struggling with innumerable health concerns that have claimed the lives of many. Wars, and the chaos they leave behind, often provide the optimal conditions for the growth and re-emergence of communicable diseases. In this article, we will highlight three of the major re-emerging vaccine preventable diseases cholera, measles, and polio, in four countries of the Eastern Mediterranean Region that are currently affected by war leading to a migration crisis: Iraq, South Sudan, Syria, and Yemen. The re…
The Eradication of Poliomyelitis in Spain: Projects, Obstacles, Achievements, Realities
2015
he main aim of our paper is to provide a historical approach to the complex process undertaken in Spain to achieve the official WHO certificate of polio eradication in 2002, within the framework of the initiatives launched in the WHO European Region. At the time of the first meeting of the European Regional Commission for the Certification of Poliomyelitis Eradication in 1996, the epidemiological situation and levels of vaccination cover (over 90%) enabled Spain, like other countries, to ensure compliance with the conditions set by the World Health Organization. This showed that the country, at the end of the twentieth century, had achieved high public health standards, which is remarkable …
Apoptosis of oligodendrocytes via Fas and TNF-R1 is a key event in the induction of experimental autoimmune encephalomyelitis.
2005
Abstract In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, immunization with myelin Ags leads to demyelination and paralysis. To investigate which molecules are crucial for the pathogenesis of EAE, we specifically assessed the roles of the death receptors Fas and TNF-R1. Mice lacking Fas expression in oligodendrocytes (ODCs) were generated and crossed to TNF-R1-deficient mice. To achieve specific deletion of a loxP-flanked fas allele in ODCs, we generated a new insertion transgene, expressing the Cre recombinase specifically in ODCs. Fas inactivation alone as well as the complete absence of TNF-R1 protected mice partially from EAE induced by the imm…
Derivatives of Erythropoietin That Are Tissue Protective But Not Erythropoietic
2004
Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype–selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyeli…