Translational Research in Neurology and Neuroscience 2010

Stüve, Olaf; Kieseier, Bernd C.; Hemmer, Bernhard; Hartung, Hans Peter; Awad, Amer; Frohman, Elliot M.; Greenberg, Benjamin; Racke, Michael K.; Zamvil, Scott S.; Phillips, J. Theodore; Gold, Ralf; Chan, Andrew; Zettl, Uwe K.; Milo, Ron; Marder, Ellen; Khan, Omar; Eagar, Todd N.

doi:10.1001/archneurol.2010.158

Cited by 11 publications

(6 citation statements)

References 133 publications

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“…Repeatedly, the objectives of a publication are framed in a broad way, whereas the endpoints chosen in the described research address narrow gaps only. Stüve et al [ 75 ] for example, review the advances in ‘translational research’ in the area of multiple sclerosis. A narrow view on TR becomes visible: the review centralizes the need for good animal models to evaluate newly developed therapies.…”

Section: Methodsmentioning

confidence: 99%

Beyond Bench and Bedside: Disentangling the Concept of Translational Research

Laan

Boenink

2012

Health Care Anal

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The label ‘Translational Research’ (TR) has become ever more popular in the biomedical domain in recent years. It is usually presented as an attempt to bridge a supposed gap between knowledge produced at the lab bench and its use at the clinical bedside. This is claimed to help society harvest the benefits of its investments in scientific research. The rhetorical as well as moral force of the label TR obscure, however, that it is actually used in very different ways. In this paper, we analyse the scientific discourse on TR, with the aim to disentangle and critically evaluate the different meanings of the label. We start with a brief reconstruction of the history of the concept. Subsequently, we unravel how the label is actually used in a sample of scientific publications on TR and examine the presuppositions implied by different views of TR. We argue that it is useful to distinguish different views of TR on the basis of three dimensions, related to (1) the construction of the ‘translational gap’; (2) the model of the translational process; and (3) the cause of the perceived translational gap. We conclude that the motive to make society benefit from its investments in biomedical science may be laudable, but that it is doubtful whether the dominant views of TR will contribute to this end.

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Section: Methodsmentioning

confidence: 99%

Beyond Bench and Bedside: Disentangling the Concept of Translational Research

Laan

Boenink

2012

Health Care Anal

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“…Thus there is a crucial need for new therapeutic targets for MS, particularly for the debilitating progressive phase, which may be identified in animal models of MS. The most widely used animal model of MS is experimental autoimmune encephalomyelitis (EAE) (5, 6). EAE is induced in susceptible rodents by immunization with myelin antigens, such as myelin-oligodendrocyte glycoprotein peptide 35-55 (MOG 35-55 ) and proteolipid protein peptide 139-151 (PLP 139-151 ), which produces disease symptoms with many similarities to MS pathology (7).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Th1 Cells and Experimental Autoimmune Encephalomyelitis by Glycogen Synthase Kinase-3

Beurel

Kaidanovich-Beilin

Yeh

et al. 2013

The Journal of Immunology

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Experimental autoimmune encephalomyelitis (EAE) is a rodent model of multiple sclerosis (MS), a debilitating autoimmune disease of the central nervous system, for which only limited therapeutic interventions are available. Since MS is mediated in part by autoreactive T cells, particularly Th17 and Th1 cells, in the present study, we tested if inhibitors of glycogen synthase kinase-3 (GSK3), previously reported to reduce Th17 cell generation, also alter Th1 cell production or ameliorate EAE. GSK3 inhibitors were found to impede the production of Th1 cells by reducing STAT1 activation. Molecularly reducing the expression of either of the two GSK3 isoforms demonstrated that Th17 cell production was sensitive to reduced levels of GSK3β, and Th1 cell production was inhibited in GSK3α-deficient cells. Administration of the selective GSK3 inhibitors TDZD-8, VP2.51, VP0.7, or L803-mts, significantly reduced the clinical symptoms of MOG35-55-induced EAE in mice, nearly eliminating the chronic progressive phase, and reduced the number of Th17 and Th1 cells in the spinal cord. Administration of TDZD-8 or L803-mts after the initial disease episode ameliorated clinical symptoms in a relapsing/remitting model of PLP139-151-induced EAE. Furthermore, deletion of GSK3β specifically in T cells was sufficient to ameliorate MOG35-55-induced EAE. These results demonstrate isoform-selective effects of GSK3 on T cell generation, therapeutic effects of GSK3 inhibitors in EAE, and that GSK3 inhibition in T cells is sufficient to reduce the severity of EAE, suggesting that GSK3 may be a feasible target for developing new therapeutic interventions for MS.

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“…Multiple sclerosis is the most common inflammatory demyelinating disease of the CNS and is widely considered an autoimmune disease caused by autoreactive T cells [13] , [14] . Several of the clinical, immunological, and neuropathological features of MS are modeled in experimental autoimmune encephalomyelitis (EAE), which is induced in susceptible mice by eliciting an immune response to injected myelin antigens [15] , [16] . The two major populations of effector T helper (Th) cells present in the CNS of mice that are thought to contribute to EAE are interferon-γ (IFNγ)-producing Th1 cells and interleukin-17A (IL-17A)-producing Th17 cells.…”

Section: Introductionmentioning

confidence: 99%

Astrocytes Modulate the Polarization of CD4+ T Cells to Th1 Cells

et al. 2014

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T-cell characteristics are dynamic and influenced by multiple factors. To test whether cells and the environment in the central nervous system (CNS) can influence T-cells, we tested if culturing mouse CD4+ T-cells on mouse primary astrocytes, compared with standard feeder cells, modified T-cell polarization to Th1 and Treg subtypes. Astrocytes supported the production of Th1 cells and Tregs, which was diminished by inflammatory activation of astrocytes, and glutamate accumulation that may result from impaired glutamate uptake by astrocytes strongly promoted Th1 production. These results demonstrate that astrocytes and the environment in the CNS have the capacity to regulate T-cell characteristics.

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Translational Research in Neurology and Neuroscience 2010

Cited by 11 publications

References 133 publications

Beyond Bench and Bedside: Disentangling the Concept of Translational Research

Beyond Bench and Bedside: Disentangling the Concept of Translational Research

Regulation of Th1 Cells and Experimental Autoimmune Encephalomyelitis by Glycogen Synthase Kinase-3

Astrocytes Modulate the Polarization of CD4+ T Cells to Th1 Cells

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