How do you measure disability in the beasties

Gilli F, Royce DB, Pachner AR. Measuring Progressive Neurological Disability in a Mouse Model of Multiple Sclerosis. J Vis Exp. 2016; (117).

After intracerebral infection with the Theiler’s Murine Encephalomyelitis Virus (TMEV), susceptible SJL mice develop a chronic-progressive demyelinating disease, with clinical features similar to the progressive forms of multiple sclerosis (MS). The mice show progressive disability with loss of motor and sensory functions, which can be assessed with multiple apparatuses and protocols. Among them, the Rotarod performance test is a very common behavioral test, its advantage being that it provides objective measurements, but it is often used assuming that it is straightforward and simple. In contrast to visual scoring systems used in some models of MS, which are highly subjective, the Rotarod test generates an objective, measurable, continuous variable (i.e., length of time), allowing almost perfect inter-rater concordances. However, inter-laboratory reliability is only achieved if the various testing parameters are replicated. In this manuscript, recommendations of specific testing parameters, such as size, speed, and acceleration of the rod; amount of training given to the animals; and data processing, are presented for the Rotarod test.

The rotorod is a device that is a spinning wheel and the animals use front and hindlegs to stay on it, it does from 4 rotations a minute up to 40 rotations and at some point the animals lose movement co-ordination and drop from the wheel and the device has a sensor and allows it to time the amount of time taken for the animals to fall. 

It is a measure of motor co-ordination and fatiguability

This paper is telling us again, something we found out many years ago….that the capacility to stay on the accelerating rotorod i a good way for measuring disability accumulation. We showed that it has very good correlation with the nerve content in the spinal cord.

Al-Izki S, Pryce G, O’Neill JK, Butter C, Giovannoni G, Amor S, Baker D. Practical guide to the induction of relapsing progressive experimental autoimmune encephalomyelitis in the Biozzi ABH mouse. Mult Scler Relat Disord. 2012;1(1):29-38.

So we use it as a way of assessing if drugs can save nerve loss. 

This was one of the reasons why MD2 was happy on friday as it looks like we found a new mechanism for neuroprotection. We will need to back this up with assessing nerve content.

We measure nerve loss by assessing the total nerve content in the spinal cord using an ELISA that ProfG and colleagues developed. 

However, unbelievably we get asked over and over a gain to show the nerve loss by histology. This is never properly quantitative as you often sample only a few sections in selected areas and not the whole cord as we measure. Our method can do a hundred samples in a maximum of two days, to do this number by histology would take nearer two-three months to do

Tell you in a few years.

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