Downregulated FPR2 expression in the epileptogenic foci of focal cortical dysplasia type IIb and tuberous sclerosis complex patients

Abstract Focal cortical dysplasia IIb (FCDIIb) and tuberous sclerosis complex (TSC) are classic pathological forms of refractory epilepsy. Increasing evidence has shown that inflammation resolution plays an important role in epilepsy. G-protein coupled formyl peptide receptor 2 (FPR2) resolves inflammation and promotes neurodevelopment by binding with resolvin D1 (RvD1), which indicates that FPR2 may be involved in epilepsy associated with FCDIIb and TSC. In this study, the expression of FPR2 and RvD1 was decreased in the epileptogenic focus and was negatively correlated with seizure frequency in FCDIIb and TSC patients. FPR2 was more widely distributed in neurons and microglia than astrocytes. Moreover, the expression levels of the RvD1 synthases 5-lipoxygenase (5-LOX) and 15-LOX were decreased in the context of FCDIIb and TSC. Activation of the NF-κB pathway in an vitro epilepsy model was inhibited by FPR2 activation using RvD1, but the FPR2 antagonist WRW4 exerted the opposite effect. Taken together, our results showed that the decreases in RvD1 and FPR2 were involved in FCDIIb and TSC with epilepsy and that FPR2 activation mediated by RvD1 contributed to inhibiting the inflammatory signaling pathway, suggesting that FPR2 activation may have a potential antiepileptic effect by restricting neuroinflammation in FCDIIb and TSC.