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Objective: To investigate the effect of (+)-borneol on neuroinflammation and microglia phenotype polarization in epileptogenesis and its possible mechanism. Methods: Based on mouse models of status epilepticus (SE) induced by pilocarpine, and treated with 15 mg/kg (+)-borneol, western-blot was used to detect the expressions of NeuN, Iba-1, TLR4, p65 and p-p65 in the hippocampus. Immunofluorescence was used to detect the expression of apoptosis-related proteins Bax and Bcl-2. To explore the effect of (+)-borneol on microglia in vitro , we used the kainic acid-induced microglia model and the concentration of (+)-borneol was 25 μM according to CCK-8 results. The levels of tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in the supernatant of each group was detected by ELISA. The nitric oxide (NO) content in the supernatant was detected by Griess method. The expressions of Iba-1 and TLR4-NFκB signaling pathway-related proteins (TLR4, p65, p-p65) were detected by Western-Blot. Immunofluorescence was used to detect microglia's M1 and M2 phenotype polarization and the expression of Iba-1 and TLR4. Results: (+)-borneol reduced hippocampal neuronal injury, apoptosis, and microglia activation by inhibiting the TLR-NFκB signaling pathway in SE mice. TLR4 agonist LPS partially reversed the neuroprotective effect of (+)-borneol. In the KA-induced microglia model, (+)-borneol inhibited microglia activation, M1 phenotype polarization, and secretion of pro-inflammatory cytokines through the TLR4-NFκB signaling pathway. LPS treatment inhibited the therapeutic effects of (+)-borneol. Conclusion: (+)-borneol inhibits microglial neuroinflammation and M1 phenotype polarization through TLR4-NFκB signaling pathway and reduces neuronal damage and apoptosis in SE mice. Therefore, (+)-borneol may be a potential drug for epilepsy modification therapy. [ABSTRACT FROM AUTHOR]

Study Objectives: Randomized controlled trials have shown that combining norepinephrine reuptake inhibitors and antimuscarinics can ameliorate the severity of obstructive sleep apnea. This article explores whether the effectiveness and safety of combining norepinephrine reuptake inhibitors with antimuscarinic agents surpass monotherapy for treating obstructive sleep apnea., Methods: We searched randomized controlled trials including adult patients with obstructive sleep apnea who received combination therapy and monotherapy in 8 databases from inception until April 5, 2023 and evaluated the studies' quality and conducted a meta-analysis and systematic review. The primary outcome was the apnea-hypopnea index. Secondary outcome measures included loop gain, hypoxic burden, oxygen desaturation index, and ventilation at low ventilatory drive, among other indicators. We assessed the quality of the studies using Cochrane Methods criteria., Results: We identified 4 randomized controlled trials for systematic review and 2 for meta-analysis. The results of the meta-analysis showed that norepinephrine reuptake inhibitors combined with antimuscarinic agents in patients with obstructive sleep apnea prolonged total sleep time by a mean of 28.20 minutes [95% confidence interval (5.78, 50.61), P = .01] and increased sleep efficiency by 4.73% [95% confidence interval (0.50, 8.97), P = .03] compared with norepinephrine reuptake inhibitors alone. Other indices and adverse events were of no statistical significance. The systematic reviews revealed that norepinephrine reuptake inhibitors combined with antimuscarinics may be superior to monotherapy in improving apnea-hypopnea index and endotypic traits., Conclusions: This evaluation demonstrated the potential advantages of combining norepinephrine reuptake inhibitors plus antimuscarinics for treating OSA compared with norepinephrine reuptake inhibitors alone and revealed no statistically significant difference in drug safety., Citation: Wang J, Ye Y, Shang Z, et al. Effect of norepinephrine reuptake inhibitors combined with antimuscarinic agents vs monotherapy for OSA: a systematic review and meta-analysis. J Clin Sleep Med . 2024;20(8):1363-1372., (© 2024 American Academy of Sleep Medicine.)