Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the earliest manifestations in human SLE, and a major cause of morbidity and mortality in this disease. While the pathways underlying NPSLE are not fully understood, blood brain barrier (BBB) disruption and altered brain perfusion have been postulated to contribute to the pathogenesis. The purpose of this study was to evaluate BBB integrity, macromolecule content, and other indicators of neurological damage in MRL-lpr/lpr mice which spontaneously develop NPSLE, compared to the background control strain MRL/+. Female MRL-lpr/lpr and MRL/+ mice were imaged by MRI at 9-10 weeks of age, at which time major neuropsychiatric symptoms including depression and cognitive dysfunction were already present. Dynamic contrast enhancement MRI indicated increased gadolinium uptake in MRL/lpr mice in all regions of the brain, with the largest differences visualized in the hypothalamus where these changes were significant. Furthemore, MRL/lpr mice displayed significantly higher concentrations of albumin, total immunoglobulin, and antibodies to double stranded DNA in their cerebrospinal fluid. In contrast, whole brain analysis of magnetic transfer contrast and quantitative T2 imaging indicated no significant differences between the MRL-lpr/lpr and MRL/+ mice. Thus, a compromised blood brain barrier (particularly in specific regions) in lupus prone MRL/lpr mice may allow for the passage of circulating autoantibodies from the serum into the brain, and induction of some of the neuropsychiatric abnormalities observed in this mouse strain. Preventing the regional breakdown in barrier integrity may be a novel approach to treatment of neuropsychiatric involvement in SLE.
- Copyright © 2013 by The American Association of Immunologists, Inc.