Comparison of the timing of acute blood-brain barrier breakdown to rabbit immunoglobulin G in the cerebellum and spinal cord of mice with experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an animal model for huma n multiple sclerosis (MS). Similar to MS patients, EAE animals can exhibit chronic or relapsing, remitting paralysis; leukocyte infiltration of the ce ntral nervous system (CNS); and breakdown of the blood-brain barrier (BBB), allowing access to serum components. EAE pathology in rodents is generally thought to progress from the spinal cord to the more rostral brain. This c ommon notion is based on numerous reports on the severity and progression o f cellular infiltration and BBB breakdown during the course of disease. We studied opening of the BBB in EAE mice immunized to the proteolipid protein (PLP) peptide, PLP 139-151, with or without the use of pertussis toxin. Pe ripherally injected rabbit immunoglobulin G showed significant penetration through a compromised BBB in EAE mice and was observed throughout the paren chyma as well as intracellularly in multiple neuronal types. Results demons trate the novel finding that the cerebellar BBB is dramatically and briefly comprised, even before breakdown of the BBB in the thoracolumbar spinal co rd and prior to symptomatic disease. The demonstration of susceptibility in the cerebellum provides an important target for studying the factors predi sposing certain CNS regions to autoimmune-related compromise of the BBB, su ch as MS. J. Comp. Neurol. 430:131-144, 2001. (C) Wiley-Liss, Inc.