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Blood-Brain Barrier Loss is Key for MS-Like Disease in Mice

Permeability correlates with disease severity, regardless of genetic makeup of mice

WEDNESDAY, March 21 (HealthDay News) -- The loss of the blood-brain barrier is an important step in the development of a multiple sclerosis-like disease in mice, according to a report published online March 19 in the Proceedings of the National Academy of Sciences Early Edition.

D. Craig Hooper, Ph.D., from Thomas Jefferson University in Philadelphia, and colleagues used mice lacking genes associated with inflammation and immunity, including NF-κB, TNF-α, IFN-αβ receptors, IFN-γ receptors, and inducible nitric oxide synthase. They determined which factors influenced the onset and severity of experimental allergic encephalomyelitis (EAE).

The investigators found that loss of the blood-brain barrier and cell accumulation in spinal cord tissues was invariably associated with EAE onset and severity, no matter which genetic model was used. Blood-brain barrier permeability, measured by the uptake of sodium-fluorescein in spinal cord fluid, was directly proportional to disease severity.

"Our findings indicate that the loss of blood-brain barrier integrity in the spinal cord is a fundamental event in the pathogenesis of EAE regardless of the genetic makeup of the mouse strain studied and that the magnitude of the neurovascular defect is generally associated with the severity of the disease," the authors write.

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