Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis

Steinman, Lawrence; Zamvil, Scott S.

doi:10.1016/j.it.2005.08.014

Cited by 240 publications

(182 citation statements)

References 67 publications

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“…The TMEV model displays a clinical outcome similar to MS, but the autoimmune response observed in MS is not described for this experimental model. By contrast, EAE presents many pathophysiological similarities to MS and is considered a more suitable model for this CNS disease 14 .…”

Section: Discussionmentioning

confidence: 99%

Mechanical hypernociception in experimental autoimmune encephalomyelitis

Rodrigues

Sachs

Teixeira

2009

Arq. Neuro-Psiquiatr.

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-Background:Pain is an important clinical manifestation in multiple sclerosis (MS) patients, though it has been neglected in clinical and experimental researches. Objective: To investigate the nociceptive response in MOG 35-55 experimental autoimmune encephalomyelitis (EAE)-induced mice. Method: EAE was induced in 8 to 10 week old C57BL/6 female mice with an emulsion of MOG , Complete Freund Adjuvant, Mycobacterium tuberculosis H37 RA and pertussis toxin. Nociception was evaluated by the von Frey filaments method. A clinical scale ranging from 0 to 15 was used to assess motor impairment. Results: Clinical evidence of disease started at day 10 and peaked at day 14 after immunization. Thereafter, there was no worsening of symptoms until day 26. The EAE-induced mice presented reduced pressure threshold at days 7 th and 10 th after immunization and before the onset of clinical motor signs. Conclusion: The hypernociception found validates MOG 35-55 EAE as a model for the study of pain in multiple sclerosis.KEY WORDS: multiple sclerosis; experimental autoimmune encephalomyelitis, hyperalgesia, mechanical hypernociception. hipernocicepção mecânica em encefalomielite autoimune experimentalResumo -Introdução: Dor é uma manifestação importante em pacientes com esclerose múltipla (EM), mas que tem sido negligenciada na pesquisas clínica e experimental. Objetivo: Investigar a resposta nociceptiva de camundongos com encefalomielite autoimune experimental (EAE) induzida por MOG . Método: A EAE foi induzida em camundongos C57BL/6 fêmeas de 8-10 semanas com emulsão contendo MOG 35-55 , Adjuvante Completo de Freund, Mycobacterium tuberculosis cepa H37 RA e toxina pertussis. A nocicepção foi medida pelo método de filamentos de von Frey. Uma escala clínica variando de 0 a 15 foi utilizada para avaliar a debilidade motora dos animais. Resultados: Os sinais clínicos da doença iniciaram-se no dia 10 e a gravidade máxima foi alcançada no dia 14 após a imunização. Não houve piora dos sintomas até o dia 26. Os camundongos induzidos com EAE apresentaram diminuição do limiar de pressão nos dias 7 e 10 após a imunização e antes do início dos sinais motores. Conclusão: A hipernocicepção verificada valida a EAE induzida por MOG 35-55 como um modelo para estudos de dor em esclerose múltipla. PALAVRAS-CHAVE: esclerose múltipla; encefalomielite autoimune experimental, hiperalgesia; hipernocicepção mecânica.

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Section: Discussionmentioning

confidence: 99%

Mechanical hypernociception in experimental autoimmune encephalomyelitis

Rodrigues

Sachs

Teixeira

2009

Arq. Neuro-Psiquiatr.

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“…Inflammation in EAE is mediated by major histocompatibility complex (MHC) class II-restricted, Th1-type CD4 + myelin reactive, and Th17-type T cells (4)(5)(6). Autoreactive T cells activate in the periphery, cross the blood-brain barrier to enter the central nervous system (CNS) and serve as important disease initiators, affecting both the local cytokine milieu and the recruitment and activation of various effector cells (7)(8)(9). Microglia and macrophages also contribute to EAE; they produce cytokines that promote inflammation during induction, but also phagocytose and clear apoptotic cell bodies, debris and inhibitory substances that limit remyelination and axon regeneration (10,11).…”

Section: Introductionmentioning

confidence: 99%

Loss of Allograft Inflammatory Factor-1 Ameliorates Experimental Autoimmune Encephalomyelitis by Limiting Encephalitogenic CD4 T-Cell Expansion

Chinnasamy

Lutz

Riascos-Bernal

et al. 2015

Mol Med

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“…Nevertheless, the EAE model has several limitations. For instance, it relies on the use of CFA as part of the immunization protocol and this adjuvant can commonly lead to confounding effects (Steinman and Zamvil, 2005). In this light, it is not surprising that the protective role of CCR2 in EAE was recently shown to be dependent on the immunization protocol and the strain of the mice used (Gaupp and Berrios, 2002).…”

Section: Introductionmentioning

confidence: 99%

Role of astrocytes and chemokine systems in acute TNFα induced demyelinating syndrome: CCR2-dependent signals promote astrocyte activation and survival via NF-κB and Akt

Quinones

Kalkonde

Estrada

et al. 2008

Molecular and Cellular Neuroscience

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Chemotactic factors known as chemokines play an important role in the pathogenesis of Multiple Sclerosis (MS). Transgenic expression of TNFα in the central nervous system (CNS) leads to the development of a demyelinating phenotype (TNFα-induced demyelination; TID) that is highly reminiscent of MS. Little is known about the role of chemokines in TID but insights derived from studying this model might extend our current understanding of MS pathogenesis and complement data derived from the classic autoimmune encephalomyelitis (EAE) model system. Here we show that in TID, chemokines and their receptors were significantly increased during the acute phases of disease. Notably, the CCL2 (MCP-1)-CCR2 axis and the closely related ligand-receptor pair CCR1-CCL3 (MIP-1α) were among the most up-regulated during disease. On the other hand, receptors like CCR3 and CCR4 were not elevated. This significant increase in the levels of chemokines/receptors correlated with robust immune infiltration of the CNS by inflammatory cells, i.e., macrophages, and immune cells particularly T and B cells. Immunostaining and confocal microscopy, along with in vitro studies revealed that astrocytes were a major source of locally produced chemokines and expressed functional chemokine receptors such as CCR2. Using an in vitro system we demonstrate Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. that expression of CCR2 was functional in astrocytes and that signaling via this receptor lead to activation of NF-kB and Akt and was associated with increased astrocyte survival. Collectively, our data suggests that transgenic murine models of MS are useful to dissect mechanisms of disease and that in these models, up-regulation of chemokines and their receptors may be key determinants in TID. NIH Public Access

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Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis

Cited by 240 publications

References 67 publications

Mechanical hypernociception in experimental autoimmune encephalomyelitis

Mechanical hypernociception in experimental autoimmune encephalomyelitis

Loss of Allograft Inflammatory Factor-1 Ameliorates Experimental Autoimmune Encephalomyelitis by Limiting Encephalitogenic CD4 T-Cell Expansion

Role of astrocytes and chemokine systems in acute TNFα induced demyelinating syndrome: CCR2-dependent signals promote astrocyte activation and survival via NF-κB and Akt

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