Abstract：
Focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC) show persistent neuroinflammation, which promotes epileptogenesis and epilepsy progression, suggesting that endogenous resolution of inflammation is inadequate to relieve neuronal network hyperexcitability. To explore the potential roles of formyl peptide receptor 2 (FPR2), which is a key regulator of inflammation resolution, in epilepsy caused by FCDIIb and TSC, we examined the expression and cellular distribution of FPR2.
The expression of FPR2 and nuclear factor-κB (NF-κB) signaling pathway was examined by real-time PCR, western blots, and analyzed via one-way analysis of variance. The distribution of FPR2 was detected using immunostaining. The expression of resolvin D1 (RvD1, the endogenous ligand of FPR2) was observed via enzyme-linked immunosorbent assay. Pearson\'s correlation test was used to evaluate the correlation between the expression levels of FPR2 and RvD1 and the clinical variants.
The expression of FPR2 was significantly lower in FCDIIb (p = .0146) and TSC (p = .0006) cortical lesions than in controls, as was the expression of RvD1 (FCDIIb: p = .00431; TSC: p = .0439). Weak FPR2 immunoreactivity was observed in dysmorphic neurons (DNs), balloon cells (BCs), and giant cells (GCs) in FCDIIb and TSC tissues. Moreover, FPR2 was mainly distributed in dysplastic neurons; it was sparse in microglia and nearly absent in astrocytes. The NF-κB pathway was significantly activated in patients with FCDIIb and TSC, and the protein level of NF-κB was negatively correlated with the protein level of FPR2 (FCDIIb: p = .00395; TSC: p = .0399). In addition, the protein level of FPR2 was negatively correlated with seizure frequency in FCDIIb (p = .0434) and TSC (p = .0351) patients.
In summary, these results showed that the expression and specific distribution of FPR2 may be involved in epilepsy caused by FCDIIb and TSC, indicating that downregulation of FPR2 mediated the dysfunction of neuroinflammation resolution in FCDIIb and TSC.
The expression of FPR2 and nuclear factor-κB (NF-κB) signaling pathway was examined by real-time PCR, western blots, and analyzed via one-way analysis of variance. The distribution of FPR2 was detected using immunostaining. The expression of resolvin D1 (RvD1, the endogenous ligand of FPR2) was observed via enzyme-linked immunosorbent assay. Pearson\'s correlation test was used to evaluate the correlation between the expression levels of FPR2 and RvD1 and the clinical variants.
The expression of FPR2 was significantly lower in FCDIIb (p = .0146) and TSC (p = .0006) cortical lesions than in controls, as was the expression of RvD1 (FCDIIb: p = .00431; TSC: p = .0439). Weak FPR2 immunoreactivity was observed in dysmorphic neurons (DNs), balloon cells (BCs), and giant cells (GCs) in FCDIIb and TSC tissues. Moreover, FPR2 was mainly distributed in dysplastic neurons; it was sparse in microglia and nearly absent in astrocytes. The NF-κB pathway was significantly activated in patients with FCDIIb and TSC, and the protein level of NF-κB was negatively correlated with the protein level of FPR2 (FCDIIb: p = .00395; TSC: p = .0399). In addition, the protein level of FPR2 was negatively correlated with seizure frequency in FCDIIb (p = .0434) and TSC (p = .0351) patients.
In summary, these results showed that the expression and specific distribution of FPR2 may be involved in epilepsy caused by FCDIIb and TSC, indicating that downregulation of FPR2 mediated the dysfunction of neuroinflammation resolution in FCDIIb and TSC.
摘要：
背景：局灶性皮质发育不良IIb型（FCDIIb）和结节性硬化症（TSC）表现出持续性神经炎症，促进癫痫发生和癫痫进展，提示炎症的内源性消退不足以缓解神经元网络兴奋过度。探讨甲酰肽受体2（FPR2）的潜在作用，这是炎症消退的关键调节剂，在由FCDIIb和TSC引起的癫痫中，我们检测了FPR2的表达和细胞分布。
方法：采用real-timePCR检测FPR2和核因子-κB(NF-κB)信号通路的表达,西方印迹,并通过单向方差分析进行分析。使用免疫染色检测FPR2的分布。通过酶联免疫吸附法观察resolvinD1（RvD1，FPR2的内源性配体）的表达。采用Pearson相关性检验评价FPR2和RvD1表达水平与临床变异的相关性。
结果：FPR2在FCDIIb（p=.0146）和TSC（p=.0006）皮质病变中的表达明显低于对照组，RvD1的表达也是如此(FCDIIb:p=.00431;TSC:p=.0439)。在畸形神经元（DN）中观察到弱FPR2免疫反应性，气球细胞（BC），FCDIIb和TSC组织中的巨细胞（GC）。此外，FPR2主要分布在发育不良的神经元中；它在小胶质细胞中稀疏，在星形胶质细胞中几乎不存在。NF-κB通路在FCDIIb和TSC患者中显著激活,NF-κB的蛋白水平与FPR2的蛋白水平呈负相关（FCDIIb：p=.00395；TSC：p=.0399）。此外,在FCDIIb(p=0.0434)和TSC(p=0.0351)患者中,FPR2蛋白水平与癫痫发作频率呈负相关.
结论：总之，这些结果表明，FPR2的表达和特异性分布可能与FCDIIb和TSC引起的癫痫有关，表明FPR2的下调介导了FCDIIb和TSC中神经炎症消退的功能障碍。
方法：采用real-timePCR检测FPR2和核因子-κB(NF-κB)信号通路的表达,西方印迹,并通过单向方差分析进行分析。使用免疫染色检测FPR2的分布。通过酶联免疫吸附法观察resolvinD1（RvD1，FPR2的内源性配体）的表达。采用Pearson相关性检验评价FPR2和RvD1表达水平与临床变异的相关性。
结果：FPR2在FCDIIb（p=.0146）和TSC（p=.0006）皮质病变中的表达明显低于对照组，RvD1的表达也是如此(FCDIIb:p=.00431;TSC:p=.0439)。在畸形神经元（DN）中观察到弱FPR2免疫反应性，气球细胞（BC），FCDIIb和TSC组织中的巨细胞（GC）。此外，FPR2主要分布在发育不良的神经元中；它在小胶质细胞中稀疏，在星形胶质细胞中几乎不存在。NF-κB通路在FCDIIb和TSC患者中显著激活,NF-κB的蛋白水平与FPR2的蛋白水平呈负相关（FCDIIb：p=.00395；TSC：p=.0399）。此外,在FCDIIb(p=0.0434)和TSC(p=0.0351)患者中,FPR2蛋白水平与癫痫发作频率呈负相关.
结论：总之，这些结果表明，FPR2的表达和特异性分布可能与FCDIIb和TSC引起的癫痫有关，表明FPR2的下调介导了FCDIIb和TSC中神经炎症消退的功能障碍。
