Specific subcortical structures are activated during seizure-induced death in a model of sudden unexpected death in epilepsy (SUDEP): A manganese enhanced magnetic resonance imaging study
Specific subcortical structures are activated during seizure-induced death in a model of sudden unexpected death in epilepsy (SUDEP): A manganese enhanced magnetic resonance imaging study
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DOI：
10.1016/j.eplepsyres.2017.05.011
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发表时间：
2017-09-01
影响因子：
2.2
通讯作者：
Faingold, Carl L.
中科院分区：
文献类型：
--
作者：
Kommajosyula, Srinivasa P.;Randall, Marcus E.;Faingold, Carl L.
癫痫猝死（SUDEP）是癫痫患者的一个主要问题。在大多数目击的SUDEP病例中，死亡前出现全身性癫痫发作和呼吸衰竭，对SUDEP患者的尸检神经影像学研究观察到特定皮质下结构的变化。我们的研究使用锰增强磁共振成像（MEMRI）检查了皮层下结构在DBA/1小鼠SUDEP模型中的作用。这些小鼠表现出声诱发的全身性癫痫发作，导致癫痫诱导的呼吸骤停（S-IRA），除非迅速进行复苏，否则会导致猝死。将声学诱导的S-IRA后DBA/1小鼠脑中的MEMRI数据与暴露于不触发癫痫发作的相同声学刺激的C57（对照）小鼠中的数据进行比较。DBA/1小鼠癫痫发作后立即将动物麻醉并断头，对照小鼠在相同时间后断头。使用14 T MRI扫描仪评价比较T1加权MEMRI图像并进行量化。与对照组相比，我们观察到DBA/1小鼠在先前涉及的听觉（上级橄榄复合体）和感觉运动边缘系统[导水管周围灰质（PAG）和杏仁核]网络以及呼吸网络结构中的活动显著增加。在某些中缝核的活动也增加了，这表明激活的naphthalonergic机制。这些数据与先前的研究结果一致，即增强5-羟色胺的作用可预防SUDEP模型中的S-IRA。PAG、呼吸核和中缝核的活动增加表明，呼吸暂停的代偿机制可能已被S-IRA激活，但不足以防止死亡。目前的研究结果表明，在DBA/1小鼠的特定皮层下结构的S-IRA诱导的变化是一致的人类SUDEP的结果。了解在动物死亡过程中大脑活动的变化可能会导致针对预防人类SUDEP的改进方法。
Sudden unexpected death in epilepsy (SUDEP) is a major concern for patients with epilepsy. In most witnessed cases of SUDEP generalized seizures and respiratory failure preceded death, and pre-mortem neuroimaging studies in SUDEP patients observed changes in specific subcortical structures. Our study examined the role of subcortical structures in the DBA/1 mouse model of SUDEP using manganese-enhanced magnetic resonance imaging (MEMRI). These mice exhibit acoustically-evoked generalized seizures leading to seizure-induced respiratory arrest (S-IRA) that results in sudden death unless resuscitation is rapidly instituted. MEMRI data in the DBA/1 mouse brain immediately after acoustically-induced S-IRA were compared to data in C57 (control) mice that were exposed to the same acoustic stimulus that did not trigger seizures. The animals were anesthetized and decapitated immediately after seizure in DBA/1 mice and after an equivalent time in control mice. Comparative T1 weighted MEMRI images were evaluated using a 14T MRI scanner and quantified. We observed significant increases in activity in DBA/1 mice as compared to controls at previously-implicated auditory (superior olivary complex) and sensorimotor-limbic [periaqueductal gray (PAG) and amygdala] networks and also in structures in the respiratory network. The activity at certain raphe nuclei was also increased, suggesting activation of serotonergic mechanisms. These data are consistent with previous findings that enhancing the action of serotonin prevents S-IRA in this SUDEP model. Increased activity in the PAG and the respiratory and raphe nuclei suggest that compensatory mechanisms for apnea may have been activated by S-IRA, but they were not sufficient to prevent death. The present findings indicate that changes induced by S-IRA in specific subcortical structures in DBA/1 mice are consistent with human SUDEP findings. Understanding the changes in brain activity during seizure-induced death in animals may lead to improved approaches directed at prevention of human SUDEP.