Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada; Departments of Pediatrics and Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
Pediatr Neurol. 2024 Dec;161:216-222. doi: 10.1016/j.pediatrneurol.2024.09.026. Epub 2024 Sep 28.
Febrile seizures affect 2% to 14% of children. Prospective studies indicate that following a relatively prolonged febrile seizure there are long-term consequences. Although controlled experiments in children have ethical limitations, nonhuman animal models give us the ability to discover new phenomena, determine their mechanisms, and test treatments that can potentially translate to the human clinical population. Rat models of febrile seizures show two temporally distinct phases: (1); behavioral seizures and (2); ongoing epileptiform activity associated with hyperoxia. The behavioral seizures mimic those displayed by children including tonic-clonic convulsions and loss of postural control. Recordings show classic spiking discharges from cortical regions during the behavioral seizures. Following behavioral seizure termination electrical recordings in rodent models reveal that there is ongoing epileptiform activity that lasts longer than the duration of the behavioral seizures themselves. This ongoing epileptiform activity is also associated with hyperoxia-levels of brain tissue oxygen well above the normoxic zone (typical oxygen levels)-and can last more than an hour. When this hyperoxia, but not the epileptiform activity, is prevented in febrile rat pups the long-term learning impairments are also prevented. This leaves important questions unanswered, "Do children also have ongoing and long-lasting epileptiform activity and associated hyperoxia following termination of their febrile behavioral seizures and does this second phase have long-term consequences"? Here we discuss appropriate animal models of febrile seizures that replicate much of the human condition with special attention to the long-term effects of occult epileptiform activity following termination of a behavioral febrile seizure.
热性惊厥影响 2%至 14%的儿童。前瞻性研究表明，在经历一次相对较长时间的热性惊厥后，会产生长期后果。虽然对儿童进行对照实验存在伦理限制，但非人类动物模型使我们能够发现新现象，确定其机制，并测试可能转化为人类临床人群的治疗方法。热性惊厥的大鼠模型显示出两个时间上明显不同的阶段：（1）行为性惊厥；（2）与高氧血症相关的持续癫痫样活动。行为性惊厥模拟了儿童表现出的惊厥，包括强直-阵挛性抽搐和姿势控制丧失。记录显示，在行为性惊厥期间皮质区域有典型的尖峰放电。在行为性惊厥终止后，在啮齿动物模型中的电记录显示存在持续的癫痫样活动，其持续时间长于行为性惊厥本身的持续时间。这种持续的癫痫样活动也与高氧血症有关——脑组织的氧水平远高于正常氧区（典型的氧水平），可持续一个多小时。当这种高氧血症，而不是癫痫样活动，在发热的幼鼠中得到预防时，长期学习障碍也得到预防。这留下了一些重要的问题没有答案：“儿童在终止热性行为性惊厥后是否也存在持续且持久的癫痫样活动和相关的高氧血症，以及这第二阶段是否存在长期后果”？在这里，我们讨论了复制人类热性惊厥状况的适当动物模型，特别关注行为性热性惊厥终止后隐匿性癫痫样活动的长期影响。
