Immunology researchers at the Kimmel Cancer Center at Jefferson studying a multiple sclerosis (MS)-like disease in mice have shown that the amount of "damage" to the central nervous system's protective blood-brain barrier, in essence, opening it, almost always correlates to the severity of the disease.
The findings, reported online in the Proceedings of the National Academy of Sciences, can be used for testing potential MS therapies and for better understanding the role of the blood-brain barrier in disease processes.
Scientists led by D. Craig Hooper, Ph.D., associate professor of cancer biology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and Hilary Koprowski, M.D., professor of cancer biology at Jefferson Medical College and director of Jefferson's Center for Neurovirology and the Biotechnology Foundation Laboratories, wanted to find out what factors might affect the onset and severity of EAE (experimental allergic encephalomyelitis), an MS-like autoimmune disease often used as a model. They studied various strains of mice, each lacking some genes associated with inflammation and immunity, and looked at what happened to the blood-brain barrier.
They discovered that the amount of blood-brain barrier damage and subsequent permeability increase correlated to the severity of disease, and surprisingly, in nearly every case, the mouse's genetic make-up didn't matter. The mice developed EAE even without supposedly crucial factors in inflammation and autoimmunity and disease.
"We've now shown in all of these mice missing certain components of the immune system that, as expected, opening the blood-brain barrier and letting cells and factors in from the circulation is critical to the development of disease," Dr. Hooper says. "The fact that the extent of the permeability change correlates with the severity of clinical disease signs shows that this is an important element in determining how sick these animals can get.
"This puts an emphasis on the fact that blood brain permeability changes are an important aspect of the development of a CNS inflammatory disease like EAE, an animal model of MS," he says.