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Mechanisms of neuropsychiatric lupus: The relative roles of the blood-cerebrospinal fluid barrier versus blood-brain barrier.


ABSTRACT: The pathogenesis of neuropsychiatric lupus (NPSLE) is believed to include the entry of circulating neuropathic antibodies to the brain via a pathologically permeable blood-brain barrier (BBB). Nevertheless, direct evidence of BBB pathology or mechanisms underlying BBB dysfunction is missing. Here, we examined BBB integrity in an established NPSLE mouse model (MRL/faslpr/lpr). Surprisingly, challenging the barrier with various exogenous tracers demonstrated insignificant changes in BBB permeability. Furthermore, electron microscopy showed no ultrastructure changes supporting hyper-permeability. However, we found that abnormal function of the blood-cerebrospinal fluid barrier (BCSFB) in the choroid plexus underlies brain exposure to neuropathic antibodies. Considerable intrathecal lymphocyte infiltration likely occurs through the BCSFB, accompanied by epithelial hyper-permeability to antibodies. Our results challenge the commonly held view of BBB disruption in NPSLE, supporting a shift in focus to BCSFB dysfunction as a causative factor in the disease.

SUBMITTER: Gelb S 

PROVIDER: S-EPMC5994369 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Mechanisms of neuropsychiatric lupus: The relative roles of the blood-cerebrospinal fluid barrier versus blood-brain barrier.

Gelb Sivan S   Stock Ariel D AD   Anzi Shira S   Putterman Chaim C   Ben-Zvi Ayal A  

Journal of autoimmunity 20180404


The pathogenesis of neuropsychiatric lupus (NPSLE) is believed to include the entry of circulating neuropathic antibodies to the brain via a pathologically permeable blood-brain barrier (BBB). Nevertheless, direct evidence of BBB pathology or mechanisms underlying BBB dysfunction is missing. Here, we examined BBB integrity in an established NPSLE mouse model (MRL/fas<sup>lpr/lpr</sup>). Surprisingly, challenging the barrier with various exogenous tracers demonstrated insignificant changes in BBB  ...[more]

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