Lipopolysaccharide potentiates hyperthermia-induced seizures.
Lipopolysaccharide potentiates hyperthermia-induced seizures.
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DOI：
10.1002/brb3.348
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发表时间：
2015-08
影响因子：
3.1
通讯作者：
Koh S
中科院分区：
文献类型：
--
作者：
Eun BL;Abraham J;Mlsna L;Kim MJ;Koh S
长时间的热性惊厥（FS）对发育中的大脑有急性和长期的影响。由于FS通常与外周感染相关，我们旨在开发一种模拟发热和免疫激活的FS临床前模型，以促进幼儿长期FS后靶向治疗的实施。出生后14天的大鼠和小鼠在用吹风机或热灯诱发高热惊厥（HT）前2 ~ 2.5h分别给予先天免疫激活剂脂多糖（LPS）200 μ g/kg和100 μg/kg。为了确定感染的模拟是否增强神经元兴奋性，量化癫痫发作的潜伏期、阈值温度和癫痫发作的总数。行为性癫痫发作与大鼠仔鼠的脑电图变化相关。在HT后的不同时间点在血液样品中评估癫痫发作诱导的促炎细胞因子产生。使用Cx 3cr 1GFP/+小鼠定量海马中癫痫发作诱导的小胶质细胞活化。脂多糖引发增加了大鼠和小鼠对高热癫痫发作的易感性，并增强了癫痫诱导的促炎细胞因子产生和小胶质细胞活化。外周炎症似乎与高热协同作用，以增强癫痫发作并加剧癫痫诱导的免疫反应。通过模拟发热，从免疫挑战调节体温升高，我们开发了一个更临床相关的动物模型，延长FS。
Prolonged febrile seizures (FS) have both acute and long-lasting effects on the developing brain. Because FS are often associated with peripheral infection, we aimed to develop a preclinical model of FS that simulates fever and immune activation in order to facilitate the implementation of targeted therapy after prolonged FS in young children. The innate immune activator lipopolysaccharide (LPS) was administered to postnatal day 14 rat (200 μg/kg) and mouse (100 μg/kg) pups 2–2.5 h prior to hyperthermic seizures (HT) induced by hair dryer or heat lamp. To determine whether simulation of infection enhances neuronal excitability, latency to seizure onset, threshold temperature and total number of seizures were quantified. Behavioral seizures were correlated with electroencephalographic changes in rat pups. Seizure-induced proinflammatory cytokine production was assessed in blood samples at various time points after HT. Seizure-induced microglia activation in the hippocampus was quantified using Cx3cr1GFP/+ mice. Lipopolysaccharide priming increased susceptibility of rats and mice to hyperthemic seizures and enhanced seizure-induced proinflammatory cytokine production and microglial activation. Peripheral inflammation appears to work synergistically with hyperthermia to potentiate seizures and to exacerbate seizure-induced immune responses. By simulating fever, a regulated increase in body temperature from an immune challenge, we developed a more clinically relevant animal model of prolonged FS.