High mobility group box 1 enhances hyperthermia-induced seizures and secondary epilepsy associated with prolonged hyperthermia-induced seizures in developing rats
High mobility group box 1 enhances hyperthermia-induced seizures and secondary epilepsy associated with prolonged hyperthermia-induced seizures in developing rats
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DOI：
10.1007/s11011-017-0103-4
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发表时间：
2017-12-01
影响因子：
3.6
通讯作者：
Fukuda, Mitsumasa
中科院分区：
文献类型：
--
作者：
Ito, Masanori;Takahashi, Hisaaki;Fukuda, Mitsumasa
高迁移率族蛋白1（HMGB 1）是一种重要的炎症介质，在热性惊厥（FS）患者血清中的水平较高。然而，其在FS和继发性癫痫后，长期FS的作用知之甚少。我们证明了HMGB 1在高血压诱导的癫痫发作（HS）和长期高血压诱导的癫痫发作（pHS）后继发性癫痫的发病机制中的作用。第一个实验中，14-15日龄雄性大鼠分为四组：高剂量HMGB 1（100 μ g）、中剂量（10 μ g）、低剂量（1 μ g）和对照组。在诱导HS前1 h，鼻内给予每只大鼠HMGB 1。在癫痫发作时用脑电图（EEG）测量体温。第二个实验将10-11日龄大鼠分为4组：pHS + HMGB 1（10 μ g）组、pHS + HMGB 1组和对照组。在pHS后24 h给予HMGB 1。在90和120日龄时记录24小时的视频脑电图;在150日龄时进行组织学分析。在第一个实验中，癫痫发作时的温度在高剂量和中等剂量HMGB 1组中显著低于对照组。在第二个实验中，自发性癫痫发作的发生率在pHS + HMGB 1组中显著高于其他组。pHS + HMGB 1组与无癫痫组之间的比较显示，癫痫大鼠在海马和胼胝体中具有显著增强的星形胶质细胞增生。在发育中的大鼠中，HMGB 1增强HS和pHS后的继发性癫痫。我们的研究结果表明，HMGB 1有助于FS的发病机制，并在获得性癫痫的继发性癫痫与延长FS的重要作用。
Levels of high mobility group box 1 (HMGB1), an important inflammatory mediator, are high in the serum of febrile seizure (FS) patients. However, its roles in FS and secondary epilepsy after prolonged FS are poorly understood. We demonstrate HMGB1's role in the pathogenesis of hyperthermia-induced seizures (HS) and secondary epilepsy after prolonged hyperthermia-induced seizures (pHS). In the first experiment, 14-15-day-old male rats were divided into four groups: high-dose HMGB1 (100 mu g), moderate-dose (10 mu g), low-dose (1 mu g), and control. Each rat was administered HMGB1 intranasally 1 h before inducing HS. Temperature was measured at seizure onset with electroencephalography (EEG). In the second experiment, 10-11-day-old rats were divided into four groups: pHS + HMGB1 (10 mu g), pHS, HMGB1, and control. HMGB1 was administered 24 h after pHS. Video-EEGs were recorded for 24 h at 90 and 120 days old; histological analysis was performed at 150 days old. In the first experiment, the temperature at seizure onset was significantly lower in the high- and moderate-dose HMGB1 groups than in the control group. In the second experiment, the incidence of spontaneous epileptic seizure was significantly higher in the pHS + HMGB1 group than in the other groups. Comparison between pHS + HMGB1 groups with and without epilepsy revealed that epileptic rats had significantly enhanced astrocytosis in the hippocampus and corpus callosum. In developing rats, HMGB1 enhanced HS and secondary epilepsy after pHS. Our findings suggest that HMGB1 contributes to FS pathogenesis and plays an important role in the acquired epileptogenesis of secondary epilepsy associated with prolonged FS.