S2B-5 Rapid Release of GABA Inhibiting Epilepsy in Vivo

Objective:Epilepsy is a multi-etiological brain dysfunction syndrome characterized by synchronously repeated spontaneous discharges from neuronal cells.Its pathogenesis involves excitatory/inhibitory imbalance,ion channel abnormalities and may be related to the abnormal structure and function of neurotransmitter receptors.The research was to observe the effects of rapid increase inhbitory neurotransmitter GABA on the excitatory/inhibitory imbalance,ion channel abnormalities and abnormal neurotransmitter receptors in living epileptic mice from the level of free moving animal,cell,sub-cell and receptor.Methods:The techniques of fiber photometry and laser uncage of Rub-GABA for epileptic free moving mice induced by administration of Kainic acid(KA)or 4-AP,local field potentials(LFP),multicell bolus lording of calcium(OGB-1AM),virus transfection of calcium-sensitive protein GCaMP6f,transfection of fluorescent labeled AMPA receptors in cortical neurons by in utero electroporation,two-photon uncage of Rubi-GABA,two-photon imaging,two-photon calcium imaging,twophoton cell attach,two-photon targeted patch clamp and two-photon shadow patch clamp in living epileptic mice induced by 4-AP were used.Results:Laser photolysis of Rubi-GABA in hippocampal CA1 could immediately alleviate KA induced acute epileptic seizures in living mice.In cellular level,two-photon uncage Rub-GABA or rapid release of GABA significantly decreased the number of neurons releasing the calcium signals by multicell bolus lording of calcium,inhibited spikes recording by LFP and immediately inhibited both calcium signals and spikes using two-photon cell attaching technique in the living epileptic mice induced by 4-AP.Two-photon uncage Rub-GABA significantly decreased spikes induced by 4-AP recording with two-photon shadow patch clamp in vivo.In sub-cellular level,two-photon Rubi-GABA uncage of dendritic spines of cortical neurons transfected with GCaMP6f obviously decreased the frequency and amplitude of calcium signal on those dendritic spines in 4-AP induced epileptic living mice.Two-photon targeted patch clamp and shadow patch clamp were performed separately to both the cortical neurons transfected fluorescent labeled AMPA receptors in the mice by in utero electroporation and the cortical neurons with no fluorescent labeled AMPA receptors in control mice.The results showed that there was no difference in the electrophysiological indices between the two kinds of cortical neurons,meaning that there was no obvious change of electrophysiological characteristics in the cortical neurons transfected fluorescent labeled AMPA receptors.Further study showed that rapid disappearance of the AMPA receptors was found before disappearance of dendritic spines in epileptic living mice induced by high concentration of 4-AP,and the disappearance of the AMPA receptors was significantly delayed or the AMPA receptors even reappeared after rapid release of GABA with the different concentration of 4-AP in the living mice.Conlusion:Rapid release of GABA can rectify the excitatory/inhibitory imbalance and ion channel abnormalities of epilepsy,and rapidly inhibits epilepsy in free moving mice,and from cellular and sub-cellular level in vivo.It also protects the structure and function of neurotransmitter receptors during epilepsy in vivo.

2017—2020年山东某高校水痘疫情流行及危险因素研究

目的 分析大学生水痘流行病学特征及相关危险因素,为高校大学生水痘的预防控制提供理论依据。方法 以2017年—2020年山东某高校确诊的大学生水痘患者为基础,采用描述性流行病学方法分析大学生水痘的流行特点,并采用病例对照研究方法,调查病例组、对照组研究对象的基本情况及相关影响因素,采用单因素及多因素logistic回归分析大学生水痘发病的危险因素。结果 2017年1月—2020年12月共确诊水痘学生198人,发病率为1.50‰;其中,2018年发病率最高(2.36‰),2020年度发病率最低(0.90‰),各年度发病率差异有统计学意义(χ^(2)=32.003,P<0.001)。水痘发病月分布分析发现,水痘发病较多的月份依次为12月(27.27%)、11月(25.25%)、4月(13.13%),发病较少的月份为8月(0.00%)、7月(1.01%),2月(1.52%)。确诊水痘学生中,散发病例79例(39.90%),聚集/暴发病例119例(60.10%);共发生聚集/暴发77起。接种疫苗者(突破病例)64例(32.32%),未接种疫苗(无免疫史)者134例(67.68%);且突破病例体温≥38.5℃及发热比例均明显低于无免疫史病例,差异均有统计学意义(χ^(2)=7.110,P=0.008;χ^(2)=9.188,P=0.002);皮疹<50个比例明显高于无免疫史患者,差异有统计学意义(χ^(2)=25.877,P<0.001);皮疹结痂时间明显缩短,差异有统计学意义[(6.04±4.08)vs(8.12±5.46),t=2.707,P=0.044]。对水痘发病危险因素进行分析发现,水痘病例接触史(OR=16.494)、带状疱疹病例接触史(OR=5.680)、医院暴露史(OR=3.655)及洗手频率(≤5次/天)(OR=3.216)是水痘发病的危险性因素(均P<0.05);接种过水痘疫苗(OR=0.418)、选修传染病健康教育课/参加传染病健康教育讲座(OR=0.704)是水痘发病的保护性因素(均P<0.05)。结论 大学生水痘发病率较高,且多数病例为聚集/暴发发病;控制大学校园水痘发病,除提高水痘疫苗接种率,还应加强手卫生及传染病健康教育宣传,注重密闭空间的通风和消毒。