Brain inflammation is one of the main causes of epileptogenesis, a chronic process triggered by various insults, including genetic or acquired factors that enhance susceptibility to seizures. Amentoflavone, a naturally occurring biflavonoid compound that has anti-inflammatory effects, exerts neuroprotective effects against nervous system diseases. In the present study, we aimed to investigate the effects of amentoflavone on epilepsy in vivo and in vitro and elucidate the underlying mechanism. The chronic epilepsy model and BV2 microglial cellular inflammation model were established by pentylenetetrazole (PTZ) kindling or lipopolysaccharide (LPS) stimulation. Cognitive dysfunction was tested by Morris water maze while hippocampal neuronal apoptosis was evaluated by immunofluorescence staining. The levels of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome complexes and inflammatory cytokines were determined using quantitative real-time polymerase chain reaction, Western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay. Amentoflavone reduced seizure susceptibility, minimized PTZ-induced cognitive dysfunction, and blocked the apoptosis of hippocampal neurons in PTZ-induced kindling mice. Amentoflavone also inhibited the activation of the NLRP3 inflammasome and decreased the levels of inflammatory cytokines in the hippocampus of PTZ-induced kindling mice. Additionally, amentoflavone could alleviate the LPS-induced inflammatory response by inhibiting the NLRP3 inflammasome in LPS-induced BV2 microglial cells. Our results indicated that amentoflavone affects epileptogenesis and exerts neuroprotective effects by inhibiting the NLRP3 inflammasome and, thus, mediating the inflammatory process in PTZ-induced kindling mice and LPS-induced BV2 microglial cells. Therefore, amentoflavone may be a potential treatment option for epilepsy.

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PurposeTo explore the value of F-NLR-AGR score based on preoperative fibrinogen, neutrophil to lymphocyte ratio (NLR), and albumin to globulin ratio (AGR) in predicting the prognosis in patients with glioma.Patients and methods203 glioma patients were retrospectively analyzed. Receiver-operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values for NLR, AGR, and fibrinogen. According to these cut-off values, patients with high NLR (>1.90), low AGR (<1.54), and elevated fibrinogen (>2.61 g/L) were defined as a score of 3, if none of the patients’ three parameters met these standards they were given a score of 0, if any two or one parameter met these standards they were scored as 2 or 1, respectively. The correlation between F-NLR-AGR score and glioma grade was also evaluated.ResultsThe three-year overall survival (OS) rate and the mean overall survival in patients with F-NLR-AGR=3 were lower than those of patients with F-NLR-AGR = 2, 1 or 0 [17.6% vs 35.2%, 66.9% or 83.7% (26.0 vs 39.0, 64.0 or 81.0 months), P<0.001]. Multivariate analysis revealed that age (HR=2.071; 95% CI=1.195–3.588; P=0.009), WHO grade (P<0.001), and F-NLR-AGR score (P<0.001) were independent prognostic factors for OS. Spearman’s rank correlation analysis revealed that F-NLR-AGR score was positively correlated with glioma grade (r=0.278, P<0.01).ConclusionPreoperative F-NLR-AGR score was correlated with glioma grading, high F-NLR-AGR score was an independent predictor of poor prognosis in glioma. Therefore, the scoring system may be applied in clinical practice to identify high-risk patients.

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Moreover, liraglutide protected against Scn1a KO-induced apoptosis, which was manifested in the phosphorylation of mTOR (KO+NS: 1.99 ± 0.31 vs. KO+Lira: 0.97 ± 0.18, P = 0.0004), as well as the downregulation of cleaved caspase-3 (KO+NS: 0.49 ± 0.04 vs. KO+Lira: 0.30 ± 0.01, P = 0.0003) and restoration of the imbalance between BAX (KO+NS: 0.90 ± 0.02 vs. KO +Lira: 0.75 ± 0.04, P = 0.0005) and BCL-2 (KO+NS: 0.46 ± 0.02 vs. KO+Lira: 0.61 ± 0.02, P = 0.0006). Collectively, these results show that liraglutide reduces seizure susceptibility and cognitive dysfunction in the mouse model of Dravet syndrome, and exerts anti-apoptotic and neuroprotective effects in Scn1a KO mice and cells.