Sunday, 3 May 2015

Atrophy in mice..A model for Progressive MS

Paz Soldán MM, Raman MR, Gamez JD, Lohrey AK, Chen Y, Pirko I, Johnson AJ. Correlation of Brain Atrophy, Disability, and Spinal Cord Atrophy in a Murine Model of Multiple Sclerosis.
J Neuroimaging. 2015 Apr 20. doi: 10.1111/jon.12250. [Epub ahead of print]

BACKGROUND: Disability progression in multiple sclerosis (MS) remains incompletely understood. Unlike lesional measures, central nervous system atrophy has a strong correlation with disability. Theiler's murine encephalomyelitis virus infection in SJL/J mice is an established model of progressive MS. We utilized in vivo MRI to quantify brain and spinal cord atrophy in this model and analyzed the temporal relationship between atrophy and disability.
METHODS: Infected and control mice were followed for 12 months. Disability was assessed periodically using rotarod assay. Volumetric MRI datasets were acquired at 7 Tesla. Ventricular volume and C4-5 spinal cord cross-sectional area measurements were performed using Analyze 10.
RESULTS: At 3 months, brain atrophy reached statistical significance (P = .005). In contrast, disability did not differ until 4 months post-infection (P = .0005). Cord atrophy reached significance by 9 months (P = 0.009). By 12 months, brain atrophy resulted in 111.8% increased ventricular volume (P = .00003), while spinal cord cross-sectional area was 25.6% reduced (P = .001) among cases.
CONCLUSIONS: Our results suggest that significant brain atrophy precedes and predicts the development of disability, while spinal cord atrophy occurs late and correlates with severe disability. The observed temporal relationship establishes a framework for mechanisms of disability progression and enables further investigations of their underlying substrate.

Today's post is really for neuros and Researchers. "Theiler's murine encephalomyelitis virus infection in SJL/J mice is an established model of progressive MS".....Says who? 

It  is indeed an established model of viral induced demyelination. However, whether it is established model for progression, we will see.  In this study the authors looked for brain and spinal cord loss and MS and found that this increased and was detected with disease duration. It was found that disability occurred with time just like MS and disability occurred before they detected it with MRI, just as occurs in MS. It shows us that some cure MRI measures only see the tip of the iceberg.  We know this by using different measures of nerve loss in animals, so whilst the atrophy of say the spinal cord only drops by 5%  or less there can be a 40% global nerve and a even greater local nerve loss by histology. So in an animals and humans we can be confident that nerve loss is associated with disability. So the model may indeed be useful to probe progressive MS...but this depends more on the researcher than the model.

Progressive MS model is one of those terms that is spread around by EAEologists.. where there models are probably nothing more that just a one hit immune lesion with poor recovery model and has as must relevance to progressive MS as one of those BlackAdder-much used sayings that "This is as much use as......" 

One question you can ask....Does progressive MS react to T cell immunotherapy...where the answer is largerly NO and does progressive animal model respond to T cell immunotherapy and the answer is invariably YES.  

So the model has no internal validity. Therefore if you pin your hopes on these models to give you the answer. To find it is asmuch by luck and chance rather than by Grand design. 

As such the EAEologists need to have a course on MS, because if you ask them to describe MS, they describe EAE. So out comes a metallic song...Sad but true! 

You can help researchers understand what MS is, by meeting the researchers to get them to think that researching animal models is about the future and hope for new treatments and not just a disease mechanism....Sad but true!

P.S. There are many good researchers that have the the interests at the core of why they do what they do.

P.P.S. For the other researchers reading this...have a think  

P.P.S. Murine means rat too!   If you mean mouse say it:-)!

2 comments:

  1. If the alemtuzumab results genuinely demonstrate that 50% of all participants remain progression free after 10 years then why do neurologists remain sceptical?

    Someone is not being clear.

    ReplyDelete

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