Behavioral and pathological outcomes in MOG 35–55 experimental autoimmune encephalomyelitis

Jones, M. D.; Nguyen, Thien; DeBoy, Cynthia A.; Griffin, John W.; Whartenby, K.A.; Kerr, Douglas A.; Calabresi, Peter A.

doi:10.1016/j.jneuroim.2008.05.013

Cited by 88 publications

(89 citation statements)

References 33 publications

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“…We also performed a grip test that measures the strength of the forelimbs and hindlimbs separately (Fig. 1C, 1D) (30). In agreement with the disease score, CD19 mAb-treated mice showed accelerated improvement compared with the CD20 mAb-treated mice (p , 0.05 for forelimbs from day 16 to day 24; p , 0.05 for hindlimbs from day 15 to day 28).…”

Section: Cd19 Mab Is More Effective Than Cd20 Mab In Suppressing Eaesupporting

confidence: 55%

“…Clinical disease was assessed daily starting at 7 d postimmunization. Scoring was as follows: 0, no disease; 1, loss of tail tone; 2, weakness of hindlimbs; 3, partial hindlimb paralysis; 4, total hindlimb paralysis with or without forelimb paralysis; 5, moribund or death (12,30).…”

Section: Eae Inductionmentioning

confidence: 99%

“…Immunized mice were tested for grip strength performance using a wire mesh grid connected to a horizontally aligned force meter (San Diego Instruments, San Diego, CA) (30). The grid was secured at a 45˚angle, and the top rung of the grid was used for all testing.…”

Section: Grip Strength Testmentioning

confidence: 99%

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Autoreactive CD19+CD20− Plasma Cells Contribute to Disease Severity of Experimental Autoimmune Encephalomyelitis

Chen

Ireland

Davis

et al. 2016

The Journal of Immunology

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The contribution of autoantibody-producing plasma cells in multiple sclerosis (MS) remains unclear. Anti-CD20 B cell depletion effectively reduces disease activity in MS patients, but it has a minimal effect on circulating autoantibodies and oligoclonal bands in the cerebrospinal fluid. Recently we reported that MEDI551, an anti-CD19 mAb, therapeutically ameliorates experimental autoimmune encephalomyelitis (EAE), the mouse model of MS. MEDI551 potently inhibits pathogenic adaptive immune responses, including depleting autoantibody-producing plasma cells. In the present study, we demonstrated that CD19 mAb treatment ameliorates EAE more effectively than does CD20 mAb. Myelin oligodendrocyte glycoprotein–specific Abs and short-lived and long-lived autoantibody-secreting cells were nearly undetectable in the CD19 mAb–treated mice, but they remained detectable in the CD20 mAb–treated mice. Interestingly, residual disease severity in the CD20 mAb–treated animals positively correlated with the frequency of treatment-resistant plasma cells in the bone marrow. Of note, treatment-resistant plasma cells contained a substantial proportion of CD19+CD20− plasma cells, which would have otherwise been targeted by CD19 mAb. These data suggested that CD19+CD20− plasma cells spared by anti-CD20 therapy likely contribute to residual EAE severity by producing autoreactive Abs. In patients with MS, we also identified a population of CD19+CD20− B cells in the cerebrospinal fluid that would be resistant to CD20 mAb treatment.

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Section: Cd19 Mab Is More Effective Than Cd20 Mab In Suppressing Eaesupporting

confidence: 55%

Section: Eae Inductionmentioning

confidence: 99%

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Autoreactive CD19+CD20− Plasma Cells Contribute to Disease Severity of Experimental Autoimmune Encephalomyelitis

Chen

Ireland

Davis

et al. 2016

The Journal of Immunology

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“…Although clinical signs of EAE are very subtle, we found lesions in hippocampal region of the brain that could be associated to memory impairment observed while conducting the MWM test. Our results are consistent with Jones et al [24], who found that pathohistological changes in the brain occur before behavioral/clinical signs of disease. One should keep in mind that scoring of disability in EAE animals could be a subjective evaluation and potentially influenced by observer bias.…”

Section: Discussionsupporting

confidence: 93%

Influenza vaccine and learning in C57BL mice with an acute experimental autoimmune encephalomyelitis

et al. 2013

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Literature data suggest possible link between influenza vaccination and development of autoimmune processes. Therefore, the aim of the study was to investigate the effect of influenza vaccination on spatial learning in mice with experimental autoimmune encephalomyelitis (EAE). EAE was induced in eight-week-old C57BL/6J female mice by subcutaneous immunization (MOG35–55 in complete Freund’s adjuvant) and Pertussis vaccine injected intraperitoneally. Mice were vaccinated with influenza vaccine three days before MOG immunization. The hippocampal-dependent spatial learning test, Morris Water Maze test (MWM), was performed before and after EAE induction. Significant difference (P < 0.05) in the time for completing the Morris Water Maze task was found between mice with mild clinical signs of EAE when compared to other mice. However no significant difference was observed between mice with EAE and mice with EAE that were vaccinated with influenza vaccine. Hippocampal tissue lesions in EAE mice are in correlation with memory impairment. Study shows no influence of influenza vaccine on progression of clinical signs of EAE, spatial learning and memory impairment.

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“…They concluded that hyponociception was due to demyelination of small diameter fibres in the sacrococcygeal dorsal root ganglia, dorsal roots and dorsal root entry zones. However, in our EAE model, demyelination is not so evident, especially before the onset of clinical signs 20 . Hence, the hypernociception observed in our results may be caused by other pathways.…”

Section: Discussionmentioning

confidence: 64%

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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Behavioral and pathological outcomes in MOG 35–55 experimental autoimmune encephalomyelitis

Cited by 88 publications

References 33 publications

Autoreactive CD19+CD20− Plasma Cells Contribute to Disease Severity of Experimental Autoimmune Encephalomyelitis

Autoreactive CD19+CD20− Plasma Cells Contribute to Disease Severity of Experimental Autoimmune Encephalomyelitis

Influenza vaccine and learning in C57BL mice with an acute experimental autoimmune encephalomyelitis

Mechanical hypernociception in experimental autoimmune encephalomyelitis

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