Li Shuo, Adamu Alhamdu, Ye Yucai, Gao Fankai, Mi Rulin, Xue Guofang, Wang Zhaojun
Second Clinical Medical School, Shanxi Medical University, Taiyuan, China.
Department of Physiology, Shanxi Medical University, Taiyuan, China.
Front Neurosci. 2024 Nov 13;18:1497102. doi: 10.3389/fnins.2024.1497102. eCollection 2024.
To investigate the effect of (+)-borneol on neuroinflammation and microglia phenotype polarization in epileptogenesis and its possible mechanism.
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 , 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- (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.
(+)-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.
(+)-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.
探讨右旋龙脑对癫痫发生过程中神经炎症和小胶质细胞表型极化的影响及其可能机制。
基于毛果芸香碱诱导的癫痫持续状态（SE）小鼠模型，用15mg/kg右旋龙脑进行处理，采用蛋白质免疫印迹法检测海马中NeuN、Iba-1、TLR4、p65和p-p65的表达。采用免疫荧光法检测凋亡相关蛋白Bax和Bcl-2的表达。为探究右旋龙脑对小胶质细胞的影响，我们使用了海藻酸诱导的小胶质细胞模型，根据CCK-8结果，右旋龙脑的浓度为25μM。采用酶联免疫吸附测定法（ELISA）检测各组上清液中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-10（IL-10）的水平。采用格里斯法检测上清液中一氧化氮（NO）含量。采用蛋白质免疫印迹法检测Iba-1和TLR4-NFκB信号通路相关蛋白（TLR4、p65、p-p65）的表达。采用免疫荧光法检测小胶质细胞的M1和M2表型极化以及Iba-1和TLR4的表达。
右旋龙脑通过抑制SE小鼠的TLR-NFκB信号通路，减轻海马神经元损伤、凋亡和小胶质细胞活化。TLR4激动剂脂多糖（LPS）部分逆转了右旋龙脑的神经保护作用。在海藻酸诱导的小胶质细胞模型中，右旋龙脑通过TLR4-NFκB信号通路抑制小胶质细胞活化、M1表型极化和促炎细胞因子的分泌。LPS处理抑制了右旋龙脑的治疗效果。
右旋龙脑通过TLR4-NFκB信号通路抑制小胶质细胞神经炎症和M1表型极化，减轻SE小鼠的神经元损伤和凋亡。因此，右旋龙脑可能是一种潜在的癫痫改良治疗药物。
