PURPOSE: To investigate the relationship between immune cell secretion of brain-derived neurotrophic factor (BDNF) with clinical and MRI variables in multiple sclerosis (MS) patients. BACKGROUND: BDNF exerts beneficial effects on neuronal growth and repair and is secreted by both neurons and immune cells. Consequently, it may mediate the crosstalk between ...

The tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO) initiates the first and rate-limiting step of the kynurenine pathway. It is induced by proinflammatory cytokines such as interferon-beta and interferon-gamma and has established effects in the control of intracellular parasites. The recent detection of its decisive function in immune tolerance at the maternal-fetal interface ...

MS risk is associated with low vitamin D status prior to disease, and Epstein Barr virus (EBV) infection seems to be a prerequisite for MS. EBV could activate autoreactive T cells by several mechanisms, but it is not clear why this leads to MS. Only a small proportion of those ...

alphaB-crystallin (CRYAB) is the most abundant gene transcript present in early active multiple sclerosis lesions, whereas such transcripts are absent in normal brain tissue. This crystallin has anti-apoptotic and neuroprotective functions. CRYAB is the major target of CD4+ T-cell immunity to the myelin sheath from multiple sclerosis brain. The pathophysiological ...

"Multiple sclerosis is an autoimmune disease," is heard so often that it is widely accepted as fact by the current generation of students and physicians. Yet, although it is undisputed that multiple sclerosis (MS) is immune mediated, an autoimmune mechanism remains unproven. Immune-mediated tissue damage can also result from viral ...

Immune modulators, such as interferon beta (IFNB) and glatiramer acetate (GA), have focused on T cells as the primary therapeutic target. In the past few year several novel therapeutic strategies have emerged that will be reviewed here. These include treatments that modify the immune balance in general, others that inhibit ...

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease with similarities to multiple sclerosis (MS). It has been suggested that relapses of EAE and MS may be associated with, and even driven by, T cells specific for novel epitopes that are primed during the course of tissue destruction in the ...

Substantial evidence supports autoimmune activity as the etiologic mechanism underlying multiple sclerosis (MS). Both the innate and the adaptive arms of the immune system are involved in the aberrant response to several antigens associated with the myelin sheath and oligodendrocytes (OGCs) after the activation of immune cells by self- or ...

Based on the efficacy of immunomodulatory therapies in patients with multiple sclerosis (MS), much of the research and thinking about pathogenesis and treatment has traditionally focused on suppressing the immune system. Whatever the cause, recent studies have rekindled the notion that neurologic dysfunction in patients with MS relates best to ...

Multiple sclerosis is classified as an inflammatory cell-mediated autoimmune disease directed against central nervous system myelin. Different stages of disease appear to be related to different patterns of inflammation and changes on MRI. It is postulated that the lack of response to anti-inflammatory drugs in the secondary progressive stage relates ...

Intracerebral infection of susceptible mouse strains with Theiler's murine encephalomyelitis virus (TMEV) results in an immune-mediated demyelinating disease similar to human multiple sclerosis. TMEV infection is widely spread via fecal-oral routes among wild mouse populations, yet these infected mice rarely develop clinical disease. Oral vaccination has often been used to ...

Murine models of experimental autoimmune encephalomyelitis (EAE) are important vehicles for studying the effects of genetic manipulation on disease processes related to multiple sclerosis (MS). Currently, a comprehensive assessment of EAE pathogenesis with respect to inflammatory and degenerating neuronal elements is lacking. By using Fluoro-jade histochemistry to mark neurodegeneration and ...

Inflammatory T cells that are reactive to myelin protein components of the CNS play a critical role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). The authors have previously generated mice that predominantly harbor T cells transgenic for a T-cell receptor (TCR) that ...

The COX-2 inhibitors Rofecoxib (Rof) and Lumiracoxib (Lum) were evaluated in experimental autoimmune encephalomyelitis (EAE), the model of multiple sclerosis (MS). Administration of Rof and Lum significantly reduced the incidence and severity of EAE, which was associated with the inhibition of MOG 35-55 lymphocyte recall response, anti-MOG 35-55 T cell ...

Axonal damage is the major cause of irreversible neurologic disability in patients with multiple sclerosis. Although axonal damage correlates with antibodies against neurofilament light (NF-L) protein, a major component of the axonal cytoskeleton, the possible pathogenic role of autoimmunity to axonal antigens such as NF-L has so far been ignored. ...

Mitogenic growth factors play an important role in the initial stages of oligodendrocyte development, but their roles in the process of myelination itself remain less well defined. In order to study directly the effects of different growth factors on myelination, we used a purified in vitro co-culture system with dorsal ...

Disruption of myelin causes severe neurological diseases. An understanding of the mechanisms that control myelination and remyelination is needed to develop therapeutic strategies for demyelinating diseases such as multiple sclerosis (MS). Our previous finding indicating the critical involvement of the gamma chain of immunogloblin Fc receptors (FcRgamma) and Fyn signaling ...

Experimental allergic encephalomyelitis (EAE) is an inflammatory demyelinating disease of the CNS that is used to model certain parameters of multiple sclerosis. To establish the relative contributions of T cell reactivity, the loss of blood-brain barrier (BBB) integrity, CNS inflammation, and lesion formation toward the pathogenesis of EAE, we assessed ...

Multiple sclerosis (MS) is the most common cause of neurological disability in young adults. The disease is characterized by inflammatory reactions, demyelination and axonal loss in the brain, spinal cord and optic nerves. Microglia seem to play an important role in the inflammatory processes in MS, since they are found ...

The complement system is known to contribute to demyelination in multiple sclerosis and experimental autoimmune encephalomyelitis. However, there are few data concerning the natural adjuvant effect of C3d on the humoral response when it binds to myelin Ags. This study addresses the effect of C3d binding to the myelin oligodendrocyte ...

Several epidemiological investigations conducted in Sardinia, insular Italy, indicate that the strong selective pressure of malaria along the centuries may have concurred to the elevated genetic MS-risk in this region. To test such hypothesis in an experimental setting, we have compared the immune response to P. falciparum (the causative agent ...

The built environment may be responsible for making nonmotorized transportation inconvenient, resulting in declines in physical activity. However, few studies have assessed both the perceived and objectively measured environment in association with physical activity outcomes. The purpose of this study was to describe the associations between perceptions and objective measures ...

The serine protease cathepsin (Cat) G dominates the proteolytic processing of the multiple sclerosis (MS)-associated autoantigen myelin basic protein (MBP) in lysosomes from primary human B cells and dendritic cells. This is in contrast to B-lymphoblastoid cell lines, where the asparagine endopeptidase (AEP) is responsible for this task. We have ...

Roles of the B7-CD28 superfamily in the regulation of Experimental Autoimmune Encephalomyelitis<BR> The immune system must be activated to fulfill its role in destroying invading pathogens. For T cell activation to occur, T cells require two signals. The first signal comes from antigen recognition of pathogens by T cell receptors. ...

Progressive demyelination in multiple sclerosis (MS) reflects the negative balance between myelin damage and repair due to physical and molecular barriers, such as astrocytic glial scars, between oligodendrocytes and target neurons. In this paper, we show that combination therapy with paclitaxel (Taxol) plus the universal methyl-donor, vitamin B12CN (B12CN), dramatically ...

We have previously shown that intraspinal microinjection of lysophosphatidylcholine (LPC), a potent demyelinating agent, results in a rapid but brief influx of T cells (between 6 and 12 h). This is accompanied by a robust activation of macrophages/microglia that leads to demyelination by 48 h. In the present study, we ...

Sixty, relapsing remitting (RR) multiple sclerosis (MS) patients, who underwent treatment with glatiramer acetate (GA), interferon (IFN)-beta 1a, and immunoglobulins (Igs) (20 per treatment group), were assessed for levels of brain-derived neurotrophic factor (BDNF) in the supernatants of unstimulated and stimulated peripheral blood mononuclear cells (PBMCs) in the first year ...

Oxidative stress is implicated in the pathogenesis of demyelinating disorders and inflammatory responses. Heme oxygenase-1 (HO-1; HSP32) is a small heat shock protein (HSP) with enzymatic activity, which is inducible by oxidative stress. In this study we analyzed autopsy and biopsy brain samples of patients with multiple sclerosis (MS) and ...

Multiple sclerosis (MS) is a multifactorial autoimmune disease of the central nervous system with a complex immune nature and varied clinical presentation. Current therapies for MS are limited by toxicity and efficacy, so interest has now turned to specifically modulating autoreactive T-cell responses. Murine MS models, such as experimental autoimmune ...

Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterized by inflammation, demyelination, and axonal degeneration. Present therapeutic strategies for MS reduce inflammation and its destructive consequences, but are not effective in the progressive phase of the disease. There is a need for neuroprotective and restorative therapies ...

Multiple sclerosis (MS) is an inflammatory disease of the human central nervous system (CNS) which develops predominantly in young adults with certain predisposing genetic characteristics, often following exposure to initiating environmental insult(s) including viral infections. The causes of MS remain elusive and no entire cure is in sight. However, it ...

The earliest research literature addressing sub-clinical characteristics of Multiple Sclerosis was largely focused on humoral immune components, particularly antibodies in the cerebrospinal fluid of MS patients. However, two decades later, in the 1990's, T cells were established as a major component of the underlying mechanism(s) of MS pathogenesis, especially since ...

Multiple sclerosis (MS) is considered an immune-mediated disorder in which immune cells cross the blood-brain barrier to enter the central nervous system (CNS) wherein they augment the neuropathology of the disease. This chapter discusses the role of various immune cell types that contribute to the development and progression of MS. ...

RhoA is one of the best-studied members of Rho GTPases. Experimental autoimmune neuritis (EAN), which is characterized by infiltration of T cells and macrophages into the peripheral nervous system, is an autoantigen-specific T-cell-mediated animal model of human Guillain-Barré Syndrome. In this study, RhoA expression has been investigated in the dorsal/ventral ...

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that commonly affects young adults. It is characterized by demyelination and glial scaring in areas disseminated in the brain and spinal cord. These lesions alter nerve conduction and induce the disabling neurological deficits that vary with ...

Acute disseminated encephalomyelitis (ADEM) is defined as a multifocal, monophasic, demyelinating, and inflammatory disease involving the central nervous system. It typically begins within 6 weeks of an antigenic challenge such as infection or immunization. Perivenous inflammation, edema and demyelination are the pathological hallmarks of ADEM. Reactivity of T-cells against myelin ...

Myelin Oligodendrocyte Glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is the most commonly used mouse model for multiple sclerosis (MS). During the of progression of EAE, microglia, the immunocompetent cells of the brain, become activated and accumulate around demyelinated lesions. Microglial activation is mediated by the extracellular protease tissue Plasminogen Activator ...

Hundred and fifty years after the discovery of multiple sclerosis (MS), neither the etiology nor the mechanism of disease is fully charted, and current treatment has only modest effect. The conceptual understanding of MS rests on the animal model experimental autoimmune encephalomyelitis (EAE). Based on 70 years experience with EAE, ...

Neurodegeneration in multiple sclerosis (MS) is the structural correlate of permanent neurological disability in patients. The histopathological features of neurodegeneration include destruction of axons as well as apoptotic cell death of neuronal cell bodies. Therapeutic efforts to control these clinically important aspects of MS pathology showed limited success so far. ...

The alphaLbeta2 integrin adhesion molecule LFA-1 is believed to be involved in the migration of autoreactive T cells to the central nervous system across the endothelial blood-brain barrier in experimental autoimmune encephalomyelitis (EAE). Here, we demonstrate that the incidence and clinical scores of EAE in LFA-1-/- mice induced by the ...

Multiple sclerosis (MS) is pathologically characterized by inflammatory demyelination and neuronal injury. Although phagocytosis of myelin debris by microglia and macrophages in acute MS lesions is well documented, its pathophysiological significance is unclear. Using real-time quantitative PCR, flow cytometry, ELISA, and reactive oxygen species (ROS) measurement assays, we demonstrated that ...

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) of presumed autoimmune origin which develops in a genetic susceptible individual triggered by additional environmental factors. In this review we will provide an update of basic pathogenic concepts. In addition, we will discuss newly evolving concepts ...

Experimental allergic encephalomyelitis (EAE), a demyelinating disease induced in the animals parallels multiple sclerosis in human in several aspects, provides a useful model to investigate multiple sclerosis. In this study, we have therefore used this model to study functions of nerve growth factor (NGF) in EAE. NGF with considerable effects ...

The Notch receptor and its ligands are involved in myelination in central nervous system (CNS) development. Re-expression of this pathway in the adult CNS has been proposed to hamper remyelination in multiple sclerosis. Previous studies also revealed that pharmacological inhibition of Notch signaling ameliorates experimental autoimmune encephalomyelitis (EAE). However, in ...

The precise mechanisms leading to CNS inflammation and myelin destruction in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) remain the subject of intense debate. In both MS and EAE, autoantibodies (autoAbs) are thought to be involved in tissue destruction through recruiting Fc receptor (FcR)-bearing cells or direct cytotoxic ...

Multiple sclerosis (MS) is a chronic neurodegenerative disease of the CNS in which an unrelenting attack from the innate and adaptive arms of the immune system results in extensive demyelination, loss of oligodendrocytes and axonal degeneration. This review summarizes advances in the understanding of the cellular and molecular pathways involved ...

Despite transient, myelin-directed adaptive immune responses in regions of fiber tract degeneration, none of the current models of fiber tract injuries evokes disseminated demyelination, implying effective mechanisms maintaining or re-establishing immune tolerance. In fact, we have recently detected CD95L upregulation accompanied by apoptosis of leukocytes in zones of axonal degeneration ...

Impaired suppressive function of CD4(+)CD25(high) regulatory T cells (T(reg)) has been reported as a novel pathogenetic mechanism in Multiple sclerosis (MS). We addressed if high apoptosis sensitivity of MS-T(reg) could explain this functional T(reg) defect. T(reg) from treatment-naïve MS patients showed high sensitivity towards CD95Ligand-mediated apoptosis and exhibited enhanced cell ...

The extensive literature and the work from our laboratory illustrate the large number of complex processes affected by estrogen that might contribute to the striking ability of 17-beta estradiol (E2) and its derivatives to inhibit clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in mice. These effects require sustained ...

Agonists of liver X receptors (LXR), members of the nuclear hormone receptor superfamily, alter secretion of proinflammatory cytokines, suggesting potential antiinflammatory effects. A synthetic LXR agonist inhibited T-cell proliferation and cytokine release in a dose-dependent manner. Treatment of mice during induction of experimental autoimmune encephalomyelitis reduced clinical symptoms, central nervous ...