Abstract

Multiple sclerosis (MS) is a chronic demyelinating disorder of the central nervous system (CNS). Its corresponding animal model, experimental autoimmune encephalomyelitis (EAE), is widely used to understand disease pathogenesis and test novel therapeutic agents. However, existing methods to score EAE disease severity are subjective and often vary between individual researchers, making it difficult to translate findings across different studies. An enhanced automated method of disease scoring would eliminate subjectivity and reduce operator-dependent errors. Here, we used an Infra-Red Activity Monitoring System (IRAMS) to measure murine locomotor activity as a surrogate measure of disease severity and compared it to standard EAE scoring methods. In mice immunized with CNS-specific myelin antigens, we observed an inverse correlation between disease severity and mouse activity, with the IRAMS showing enhanced disease scoring compared to standard EAE scoring methods. Relative to standard EAE scoring methods, IRAMS showed comparable measurement of disease relapses and remissions in the SJL/J-relapsing-remitting model of EAE, and could comparably assess the therapeutic efficiency of the MS drug, Copaxone (Glatiramer acetate-GA). Thus, the IRAMS is a method to measure disease severity in EAE without subjective bias and is a tool to consistently assess the efficacy of novel therapeutic agents for MS.

Highlights

  • Multiple sclerosis (MS) is a chronic demyelinating disorder of the central nervous system (CNS)

  • We placed Human Leukocyte Antigen (HLA)-DR3.DQ8 transgenic (Tg) mice (8–12 weeks old) in their normal cages, and placed these within Infra-Red Activity Monitoring System (IRAMS) brackets equipped with two sensors (Columbus Instruments, Columbus, OH) (Supplemental Fig. S1) to measure both horizontal (X-axis) and vertical (Z-axis) activity during day or night

  • EAE is a widely used pre-clinical animal model of MS1–4, and its significance is highlighted by the fact that the majority of drugs that are currently utilized to treat this disease have been developed with this model[16]

Read more

Summary

Introduction

Multiple sclerosis (MS) is a chronic demyelinating disorder of the central nervous system (CNS). Our results suggest that infrared-based monitoring of nocturnal activity provides an improved assessment of quantitative motor deficits and ambulatory function and can be used as a surrogate to current scoring systems to detect disease severity in murine models of MS. This advancement in detection systems enables the field to reduce operator-dependent subjective errors and minimizes the impact of daily human handling of mice, nullifying potential bias and human-induced stress that can affect disease severity

Objectives
Methods
Results
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.