Resolvin D1'in lipopolisakkarit kaynakli kan-beyin bariyeri hasarina etkisi

The blood-brain barrier (BBB), composed of brain capillary endothelial cells, is crucial for maintaining brain homeostasis. Sepsis is a life-threatening condition that complicates severe infection, and the resultant systemic inflammatory response of the body leads to damage in multiple organs including the brain. Resolvin D1 (RvD1), a lipid mediator derived from docosahexaenoic acid, has strong anti-inflammatory and antioxidant properties. This study aimed to investigate whether RvD1 alleviates BBB disruption caused by lipopolysaccharide (LPS)-induced inflammatory condition in an in vitro model of BBB. The bEnd.3 cell monolayers were treated with LPS (500 ng/mL) and/or RvD1 (80 ng/mL) for 24 hours. The BBB integrity was assessed by transendothelial electrical resistance (TEER) measurements and sodium fluorescein (NaFl) permeability assay. Immunofluorescence staining and western blot analyses were conducted to assess the alterations in the expression of BBB-associated proteins, claudin- 5, caveolin-1, and major facilitator superfamily domain containing 2a (Mfsd2a), and inflammatory mediators, nuclear factor-κB (NF-κB), and interleukin 1 beta (IL-1β). RvD1 significantly improved BBB integrity, as evidenced by increased TEER values and decreased permeability of NaFl tracer (p < 0.0001). RvD1 administration reversed LPS- induced upregulation of caveolin-1 and downregulation of claudin-5 and Mfsd2a expression (p < 0.01). Moreover, RvD1 treatment led to decreases in the LPS-induced elevated expression levels of NF-κB and IL-1β, with the differences reaching statistical significance for the latter inflammatory mediator (p < 0.05). In conclusion, RvD1 improves BBB disruption induced by LPS via preserving tight junction integrity, regulating endothelial transcytosis, and attenuating inflammatory signaling. These findings suggest that RvD1 may prove to be a potentially promising therapeutic option for protecting BBB homeostasis under inflammatory conditions such as sepsis.