Interventions In Multiple Sclerosis Research Articles

Myelin‐induced microglial neurotoxicity can be controlled by microglial metabotropic glutamate receptors

Microglia are present in an activated state in multiple sclerosis lesions. Incubation of primary cultured rat microglia with rat-brain derived myelin (0.1-1 microg/mL) for 24 h induced microglial activation; cells displayed enhanced ED1 staining, expression of inducible nitric oxide synthase, production and release of the cytokine tumour necrosis factor-alpha and glutamate release. Exposure of microglia to myelin induced the expression of neuronal caspases and ultimately neuronal death in cultured cerebellar granule cell neurons; neurotoxicity was directly because of microglial-derived soluble toxins. Co-incubation of microglia with agonists or antagonists of different metabotropic glutamate receptor (mGluR) subtypes ameliorated microglial neurotoxicity by inhibiting soluble neurotoxin production. Activation of microglial mGluR2 exacerbated myelin-evoked neurotoxicity whilst activation of mGluR3 was protective as was activation of group III mGluRs. These data show that myelin-induced microglial neurotoxicity can be prevented by regulation of mGluRs and suggest these receptors on microglia may be promising targets for therapeutic intervention in multiple sclerosis.

The effects of non-pharmacological interventions on fatigue in four chronic illness conditions: a critical review

Central fatigue is a prevalent symptom in many neurological and non-neurological conditions. Pharmacological therapy may have limited effects on fatigue; furthermore, pharmacological therapies designed to combat primary disease may also contribute to the experience of fatigue. This review identified and critically reviewed non-pharmacological interventions, frequently or occasionally used in physiotherapy practice, for fatigue in four chronic health conditions: multiple sclerosis, Parkinson's disease, cancer and human immunovirus/autoimmune deficiency syndrome (HIV/AIDS). Despite promising evidence for the effects of aerobic and resistance exercise on fatigue in the cancer population, there is less evidence for exercise intervention in multiple sclerosis, Parkinson's disease, cancer and HIV/AIDS. There is promising evidence for energy management of fatigue in multiple sclerosis and cancer. There is little evidence for the effects of complementary and alternative interventions on fatigue in all populations and no evidence for the effects of any non-pharmacological intervention on fatigue in Parkinson's disease.

Colloquium C15: Integrins as Targets for Therapeutic Intervention in Multiple Sclerosis

Journal of NeurochemistryVolume 85, Issue s1 p. 96-96 Free Access Colloquium C15: Integrins as Targets for Therapeutic Intervention in Multiple Sclerosis First published: 07 April 2003 https://doi.org/10.1046/j.1471-4159.85.s1.30.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume85, Issues1May 2003Pages 96-96 RelatedInformation

Early intervention in multiple sclerosis : better outcomes for patients and society?

Multiple sclerosis (MS) is thought to be a chronic inflammatory disorder of the CNS. The past decade has seen the introduction of the new immunomodulatory drugs, interferon (IFN)-beta and glatiramer acetate, that have considerably improved the therapeutic options for this often disabling disease. The efficacy of these treatments in terms of reducing relapse rate and slowing progression has been proven in several large, multicentre, randomised, controlled trials. Similarly, early IFNbeta treatment of patients with clinically isolated syndromes suggestive of MS has been shown to lengthen time to conversion into definite MS. Cost-effectiveness has been questioned with the increasing use of these innovative and, therefore, costly therapies; however, modern studies with appropriate economic modelling suggest that treatment with IFNbeta may indeed be cost-effective. Since increasing disability is associated with increasing costs, stabilisation of the disease at low functional grades of disability should aim at not only improving quality of life for the individual patient, but provide for prospective cost-benefit analysis focussing on the socioeconomic aspects of MS.

Pre-emptive targeting of the epitope spreading cascade with genetically modified regulatory T cells during autoimmune demyelinating disease.

Epitope spreading or endogenous self-priming has been implicated in mediating the progression of autoimmune disease. In the present study we created an immune-deviated, epitope spreading response in SWXJ mice after the onset of experimental autoimmune encephalomyelitis, a prototypic autoimmune animal model widely used in multiple sclerosis research. We established an immunoregulatory spreading repertoire by transferring T cells genetically modified to produce high levels of IL-10 in response to a dominant epitope spreading determinant. Installation of a Th2/Tr1-like spreading repertoire resulted in a marked and prolonged inhibition of disease progression and demyelination characterized by 1) bystander inhibition of the recall response to the priming immunogen, and 2) a Th1-->Tr1 immune-deviated spreading response involving a shift in the source of IL-10 production from the transferred regulatory population to the host-derived, endogenously primed repertoire. Thus, our data provide a rationale for cell-based therapeutic intervention in multiple sclerosis by showing that pre-emptive targeting of the epitope spreading cascade with regulatory T cells effectively induces an immune-deviated spreading response capable of inhibiting ongoing inflammatory autoreactivity and disease progression.

Early Diagnosis and Intervention in Multiple Sclerosis

ABSTRACT This article provides guidelines for identifying and treating relapsing-remitting MS in the primary care setting and reviews recent additions to treatment options for disease management. Approaches for patient counseling and recommendations by the National Multiple Sclerosis Society are also discussed. (Int J MS Care. 2001; 3(3): 8–14)