Wednesday, 7 December 2016

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.

Advent Calendar 7

Tuesday, 6 December 2016

#NewsSpeak: Is Christmas time still a time for giving?

MS Society Auction; St Paul's Cathedral. Christmas 2016. #NewsSpeak #MSBlog

Thursday night kick-starts the Christmas season and there is no better way that giving to the MS Society. I will be attending the carol service and reflecting on life and what it must be like to live with MS. The MS Society is one organisation that exist to represent you the person living with the disease. If you can, I would encourage you, and your family and friends, to donate to the MS Society.

Click on picture to make a donation! 

To get in you in the Christmas mood I hope you don't mind me referencing some memorable quotes from one of my favourite books, the 'A Christmas Carol',  by Charles Dickens. It was written in 1843 and is heartwarming story of repentance, redemption, and the transformative power of love and charity.

Scrooge: “Bah, humbug!”

Narrator: “Oh! but he was a tight-fisted hand at the grindstone, Scrooge! A squeezing, wrenching, grasping, scraping, clutching, covetous old sinner!”

Scrooge: “If I could work my will, every idiot who goes about with 'Merry Christmas' on his lips should be boiled with his own pudding and buried with a stake of holly through his heart. He should!"

Scrooge’s nephew: “I am sorry for [Scrooge]. I couldn't be angry with him if I tried. Who suffers by his ill whims? Himself always.’’

Narrator: “There is nothing in the world so irresistibly contagious as laughter and good humour.”

Scrooge to the Ghost of Jacob Marley: “You may be an undigested bit of beef, a blot of mustard, a crumb of cheese, a fragment of underdone potato. There's more of gravy than of grave about you, whatever you are!"

Marley’s ghost to Scrooge: ‘’No space of regret can make amends for one life’s opportunity misused.’’

Ghost of Christmas Past: “What! Would you so soon put out, with worldly hands, the light I give?”

Scrooge: “Ghost of the Future, I fear you more than any spectre I have seen. But as I know your purpose is to do me good, and as I hope to live to be another man from what I was, I am prepared to bear you company, and do it with a thankful heart. Will you not speak to me?”

Scrooge: “I will honour Christmas in my heart, and try to keep it all the year. I will live in the Past, the Present, and the Future. The Spirits of all Three shall strive within me.’’

Scrooge: ‘’I don't know what to do! I am as light as a feather, I am as happy as an angel, I am as merry as a school-boy. I am as giddy as a drunken man. A merry Christmas to every-body! A happy New Year to all the world! Hallo here! Whoop! Hallo!”

Narrator, of Scrooge: “And it was always said of him, that he knew how to keep Christmas well, if any man alive possessed the knowledge. May that be truly said of us, and all of us!’’

Tiny Tim: God bless Us, Every One!

Happy Holidays

The Blogging Team at Barts-MS

#NewsSpeak: blowing our own trumpet

MS Reporters if you haven't watched them you are missing out! #MSReporters #NewsSpeak #MSBlog

Some of you may know that Barts-MS are part of the MS-Reporters project run by Shift.MS. The following are our annual figures that have been supplied by the charity. Good or bad we don't know. We would like to take this opportunity to than the Wellcome Trust for generoulsy funding this work. 

Advent Calendar 6