All About Multiple Sclerosis

More MS news articles for July 2003

Cerebellar susceptibility to experimental autoimmune encephalomyelitis in SJL/J mice: potential interaction of immunology with vascular anatomy

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12879974&dopt=Abstract

Cerebellum. 2002 Jan-Mar;1(1):57-68
Tonra JR.
Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.

Experimental autoimmune encephalomyelitis (EAE) is utilized as an animal model for multiple sclerosis (MS).

In both EAE and MS, activated T-lymphocytes specific for self-antigens present in myelin are linked to CNS inflammation and the breakdown of the blood-brain barrier (BBB) to peripheral blood leukocytes and plasma proteins, predominately in myelin rich white matter.

One aspect of MS that has received relatively little attention is the finding that certain CNS regions are more likely than others to develop disease in different patient populations.

Understanding the factors predisposing specific brain regions to autoimmune attack, or protecting other regions, would provide a better understanding of the disease as a process, and may also offer additional targets for therapeutic development.

EAE offers a model to search for these factors and the first step in such a process is to identify the brain regions that are susceptible to EAE.

Until recently the spinal cord in rodents has been considered the region most susceptible to EAE, with disease in more rostral regions occurring later and with reduced severity.

However a more recent study has shown that the cerebellum of SJL/J mice, like the spinal cord, is especially susceptible to BBB breakdown in EAE.

Although many factors known to be involved in BBB formation and breakdown remain to be assessed for their possible role in increasing the susceptibility of the cerebellum, one potentially important factor is the location of venules, which are the most affected vascular elements in inflamed tissue.

There is a prevalence of large EAE susceptible venules traveling in the myelin rich white matter tracts in SJL/J mouse cerebellar cortex, indicating that the vascularization of this tissue may contribute to the increased susceptibility to inflammation in response to autoimmune attacks directed against CNS myelin.