Inhibitory effect of baricitinib on microglia and STAT3 in a region with a weak blood–brain barrier in a mouse model of rheumatoid arthritis.

This article investigates the effects of baricitinib, a Janus kinase (JAK) 1 and 2 inhibitor used in rheumatoid arthritis (RA) treatment, on microglial activation and neuroinflammation in the area postrema, a brain region with a weak blood–brain barrier (BBB), using a collagen-induced arthritis (CIA) mouse model. The study found that baricitinib reduced microglial activation and phosphorylated STAT3 (signal transducers and activators of transcription 3) expression in the area postrema during the early phase of arthritis, accompanied by improvements in feeding behavior and sucrose preference, which are indicative of reduced depression-like symptoms. However, baricitinib did not affect microglial morphology or bodyweight loss in the late phase despite improving peripheral arthritis severity. These findings suggest that baricitinib may directly modulate neuroinflammation in brain regions with attenuated BBB function, potentially contributing to the alleviation of neuropsychological symptoms associated with RA.