Blood Brain Barrier Breakdown Precedes Infiltration in MS

As we discussed in class, Multiple Sclerosis is currently an idiopathic disorder with no known precipitating cause. Clinically it manifests itself as demyelinated areas of the central nervous system called lesions that contain blood derived immune monocytes. Because the immune system and the central nervous system are normally separated the immune cells are unable to discriminate between brain antigens and foreign antigens.
It is for this reason Multiple sclerosis has been considered an autoimmune disorder and therapies have centered around attempting to modify the inflammatory response and try to depress what seems to be considered an overactive immune system response. In the review article from last class by Martino and associates, it was noted that the blood brain barrier showed enhanced leakiness around the sites of the lesions but it was unknown whether this preceded or was a result of an already initiated immune response. I see this as a pivotal question to answer in the quest for a treatment of multiple sclerosis. Obviously at some point damage is done by the blood born immune system but is this behavior due to an aberrant immune response in need of correction or is it simply working perfectly against antigens that it should never have had the opportunity to encounter in the first place?
According to a paper by Floris and associates in the journal Brain, they were able to determine that in animal models with allergic encephalomyelitis (EAE) MRI imaging with gadolinium showed that vascular leakage and onset of neurological signs occurred concomitantly BEFORE the infiltration of immune monocytes. This suggests that cerebrovascular leakage and monocyte infiltration are two distinct events in the development of the lesions. This may be a very important consideration in the direction of research and the development of new therapies for multiple sclerosis.