Abstract

Background Myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for multiple sclerosis. The characteristic feature of the MOG-EAE model in Brown Norway rats is consistent involvement of the spinal cord resulting in limb paresis. The aim of the study was to investigate whether early subclinical gait abnormalities are present in this animal model and can be detected by CatWalk XT, a fully automated gait analysis system. Furthermore, we investigated the usability of CatWalk system for treatment studies.ResultsOur gait analysis showed no preclinical abnormalities in MOG-EAE animals. Nevertheless, we characterized a combination of gait parameters that display a high predictive capacity in regard to disease onset. Our detailed histopathological analysis of the spinal cord revealed that lesion formation starts in the lumbar region and propagates toward the cervical part of the spinal cord during the disease course. In the treatment study, the stabilization of gait parameters under the treatment with methylprednisolone was detected in CatWalk as well as in traditional EAE-scoring system.ConclusionsThe results from CatWalk test indicate no benefit of lab-intensive automated gait system in EAE-model with chronic-progressive disease course as well as in therapeutic studies with pronounced effect on the severity of clinical symptoms. However, due to its quantitative and objective nature this system may display a refined test to detect small but functional relevant changes in regeneration-orientated studies.

Highlights

  • Myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for multiple sclerosis

  • Because weight loss did not excess more than 10% of total body weight in any animal this phenomenon does not interfere with gait recording

  • As mentioned above the aim of the study was to quantify early, in regard to the EAE scoring paradigm subclinical abnormalities in the gait of MOG-EAE animals compared to sham-immunized control animals

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Summary

Introduction

Myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for multiple sclerosis. The aim of the study was to investigate whether early subclinical gait abnormalities are present in this animal model and can be detected by CatWalk XT, a fully automated gait analysis system. Our previous studies on the visual pathway in this animal model suggest that treatment with neuroprotective substances should be started early even in the preclinical stage of the disease [8,9,10]. In the present project we aimed to evaluate early clinically not detectable abnormalities in locomotion using automated gait analysis in MOG-immunized animals in order to identify a specific time point for the start of neuroprotective therapies. To investigate the usability of Catwalk to detect improvement of locomotion abnormalities we applied this automated behavioral test in the treatment study with methylprednisolone (Mps), a standard therapy for MS-relapses

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