Using Animals to Probe Inflammation in MS

If you Look Down A Microscope at a bit of Brain Tissue From Someone with MS, which was stained with a dye that picks up the nuclei of cells. You sometimes see accumulation of cells around blood vessels (veins)

"What are they?, How Does they Occur? Can we Stop them occurring?".

What are they?
You can stain the brain tissue from MS and see that they are white blood cells using markers on the surface of the cell. However, this is only a snap shot in time, so how do we know what is happening before and after this?

How Does this Occur?
Animal studies let you investigate this. Normally the blood brain barrier, which if formed by specialised cells in the blood vessels of the brain and the action of glial that contact the outside of the blood vessel keep out cells and blood products from entering the brain and spinal cord.

Image of Brain blood vesssel by Ben Brahim Mohammed

During disease in EAE animals you also get white blood cell cuffs around blood vessels. These develop when disease-causing white blood cells enter the brain and signal for other cells to enter the brain to cause damage.The cells in the blood vessel are stimulated to put out flags (markers), which tell white blood cells to leave the blood.

The white blood cells stick to the blood vessel wall using these flags to anchor themselves onto the blood vessel, despite the force of the blood pulsing through the veins (see how the cell above is being stretched). The cells then burrow through the blood vessel wall and then accumulate around the blood vessel before they enter the brain tissue and then damage the myelin forming cells and trigger the development of relapses.

Or another way think of it is cars (white blood cells) leaving the road (blood vessel) to get into a secure park car (brain).

Image courtesy of John Greenwood

To get in the brain, the engine of the car must be turned on (the cell must be activated). The car/driver spots the different curb at the entrance way (the flag that tells white blood cells to enter the brain) and interacts with the barrier (the blood cell signals to cells in the blood vessel). This causes the barrier to open to allow the car to enter the parkpark (The white blood cell burrows through the blood vessel and the cells in the blood vessel change their internal structure to allow this burrowing to occur. The cells get into the brain to cause EAE and MS.

Image courtesy of John Greenwood

Can we Stop Them Occurring?"
Through seeing how cells adhere to blood vessel walls during EAE, it was found that one of the flags that white blood cells stick to is called vascular cell (blood vessel) adhesion molecule one. To grasp the flag, the white blood cell use a molecule called Very Late Antigen 4.

Through blocking this molecule with a drug called Tysabri, it stopped white blood cells sticking to brain blood vessels so they couldn't enter the brain and so the development of EAE was halted.

This Drug inhibits the Development of Relapse in MS