Status epilepticus （SE） is a life-threatening neurological emergency associated with a high mortality rate. The serotonin 1A （5-HTIA） receptor is a possible target for the treatment of SE, but its role in animal m...Status epilepticus （SE） is a life-threatening neurological emergency associated with a high mortality rate. The serotonin 1A （5-HTIA） receptor is a possible target for the treatment of SE, but its role in animal models and the precise area of brain involved remain controversial. The hippocampus is a candidate site due to its key role in the development of SE and the existence of a high density of 5-HT1A receptors. Therefore, we investigated the effects of subcutaneous and intrahippocampal activation of 5-HT1A receptors in lithium-pilocarpine-induced SE, and tested whether the hippocampus is a true effector site. We developed SE in male Sprague-Dawley rats by giving lithium chloride （LiCI; 3 meq/kg, i.p.） 22-24 h prior to pilocarpine （25 mg/kg, i.p.）, and found that 8-OH-DPAT, a 5-HT1A receptor agonist administered subcutaneously （s.c.） at 0.5 or 1.0 mg/kg 1 h before pilocarpine injection increased the latency to the first epileptiform spikes, the electrographic SE, and the behavioral generalized seizures （GS）, while reducing the total EEG seizure time （P 〈0.01）. The duration of GS was shortened only by 1.0 mg/kg 8-OH-DPAT s.c. （P 〈0.05）. All these effects were inhibited by combined administration of WAY-100635 （1.0 mg/kg, s.c.） （P 〈0.05）, an antagonist of the 5-HT1A receptor, but WAY-100635 alone and low doses of 8-OH- DPAT （0.01 and 0.1 mg/kg） did not alter seizure activity. Furthermore, intrahippocampal 8-OH-DPAT only shortened the GS duration （P 〈0.05）. These findings imply that the 5-HT1A receptor is a promising therapeutic target against the generation and propagation of SE, and hippocampal receptors are involved in reducing the seizure severity.展开更多
目的：采用meta分析方法评价5-羟色胺1A受体（5-HTR1A）基因多态性与自杀行为相关的研究。方法：通过计算机检索Pub Med、Embase、Web of Science、中国生物医学文献数据库（CBM）、万方、维普、知网（CNKI）等中英文数据库,严格按照制...目的：采用meta分析方法评价5-羟色胺1A受体（5-HTR1A）基因多态性与自杀行为相关的研究。方法：通过计算机检索Pub Med、Embase、Web of Science、中国生物医学文献数据库（CBM）、万方、维普、知网（CNKI）等中英文数据库,严格按照制定的纳入与排除标准,选择5-HTR1A基因多态性与自杀行为相关病例对照研究,检索范围为2003年12月30日-2013年12月30日。采用STATA12.0软件进行meta分析,计算优势比（OR）及其95%可信区间（95%CI）,分析5-HTR1A基因多态性与自杀行为的关联性。结果：共纳入8项研究,包括1357例有自杀行为的患者及1675例正常对照。meta分析结果表明,5-HTR1A基因C〉G（-1019）多态性与自杀行为的相关有统计学意义（等位基因模型,OR=0.65,95%CI：0.46~0.92,P=0.015;显性基因模型,OR=0.76,95%CI：0.64~0.91,P=0.002）。根据种族进行亚组分析发现,在亚洲人群中5-HTR1A基因单核苷酸-1019 C/G多态性与自杀行为有显著关联（等位基因模型：OR=0.48,95%CI：0.25~0.93,P=0.029;显性基因模型：OR=0.37,95%CI：0.24~0.56,P〈0.001）;而在高加索人群中5-HTR1A基因多态性与自杀行为无显著关联（等位基因模型：OR=0.71,95%CI：0.49~1.02,P=0.065;显性基因模型：OR=0.89,95%CI：0.73~1.08,P=0.247）。结论：本meta分析的结果提示5-HTR1A基因多态性与自杀行为的发生有关,其基因多态性可能是人们产生自杀行为的一个潜在危险因素。展开更多
基金supported by grants from the National Natural Science Foundation of China (81000556, 81100968, 81171227)the Traditional Chinese Medicine Scientific Research Fund of Zhejiang Province, China (2010ZA069)
文摘Status epilepticus （SE） is a life-threatening neurological emergency associated with a high mortality rate. The serotonin 1A （5-HTIA） receptor is a possible target for the treatment of SE, but its role in animal models and the precise area of brain involved remain controversial. The hippocampus is a candidate site due to its key role in the development of SE and the existence of a high density of 5-HT1A receptors. Therefore, we investigated the effects of subcutaneous and intrahippocampal activation of 5-HT1A receptors in lithium-pilocarpine-induced SE, and tested whether the hippocampus is a true effector site. We developed SE in male Sprague-Dawley rats by giving lithium chloride （LiCI; 3 meq/kg, i.p.） 22-24 h prior to pilocarpine （25 mg/kg, i.p.）, and found that 8-OH-DPAT, a 5-HT1A receptor agonist administered subcutaneously （s.c.） at 0.5 or 1.0 mg/kg 1 h before pilocarpine injection increased the latency to the first epileptiform spikes, the electrographic SE, and the behavioral generalized seizures （GS）, while reducing the total EEG seizure time （P 〈0.01）. The duration of GS was shortened only by 1.0 mg/kg 8-OH-DPAT s.c. （P 〈0.05）. All these effects were inhibited by combined administration of WAY-100635 （1.0 mg/kg, s.c.） （P 〈0.05）, an antagonist of the 5-HT1A receptor, but WAY-100635 alone and low doses of 8-OH- DPAT （0.01 and 0.1 mg/kg） did not alter seizure activity. Furthermore, intrahippocampal 8-OH-DPAT only shortened the GS duration （P 〈0.05）. These findings imply that the 5-HT1A receptor is a promising therapeutic target against the generation and propagation of SE, and hippocampal receptors are involved in reducing the seizure severity.
文摘目的：采用meta分析方法评价5-羟色胺1A受体（5-HTR1A）基因多态性与自杀行为相关的研究。方法：通过计算机检索Pub Med、Embase、Web of Science、中国生物医学文献数据库（CBM）、万方、维普、知网（CNKI）等中英文数据库,严格按照制定的纳入与排除标准,选择5-HTR1A基因多态性与自杀行为相关病例对照研究,检索范围为2003年12月30日-2013年12月30日。采用STATA12.0软件进行meta分析,计算优势比（OR）及其95%可信区间（95%CI）,分析5-HTR1A基因多态性与自杀行为的关联性。结果：共纳入8项研究,包括1357例有自杀行为的患者及1675例正常对照。meta分析结果表明,5-HTR1A基因C〉G（-1019）多态性与自杀行为的相关有统计学意义（等位基因模型,OR=0.65,95%CI：0.46~0.92,P=0.015;显性基因模型,OR=0.76,95%CI：0.64~0.91,P=0.002）。根据种族进行亚组分析发现,在亚洲人群中5-HTR1A基因单核苷酸-1019 C/G多态性与自杀行为有显著关联（等位基因模型：OR=0.48,95%CI：0.25~0.93,P=0.029;显性基因模型：OR=0.37,95%CI：0.24~0.56,P〈0.001）;而在高加索人群中5-HTR1A基因多态性与自杀行为无显著关联（等位基因模型：OR=0.71,95%CI：0.49~1.02,P=0.065;显性基因模型：OR=0.89,95%CI：0.73~1.08,P=0.247）。结论：本meta分析的结果提示5-HTR1A基因多态性与自杀行为的发生有关,其基因多态性可能是人们产生自杀行为的一个潜在危险因素。
