Kim Eun-Hee, Yum Mi-Sun, Lee Minyoung, Kim Eun-Jin, Shim Woo-Hyun, Ko Tae-Sung
Department of Pediatrics, CHA Gangnam Medical Center, CHA University, Seoul, South Korea.
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, South Korea.
Front Neurol. 2017 Jun 12;8:271. doi: 10.3389/fneur.2017.00271. eCollection 2017.
Malformations of cortical development (MCDs) can cause medically intractable epilepsies and cognitive disabilities in children. We developed a new model of MCD-associated epileptic spasms by treating rats prenatally with methylazoxymethanol acetate (MAM) to induce cortical malformations and postnatally with -methyl-d-aspartate (NMDA) to induce spasms. To produce cortical malformations to infant rats, two dosages of MAM (15 mg/kg, intraperitoneally) were injected to pregnant rats at gestational day 15. In prenatally MAM-exposed rats and the controls, spasms were triggered by single (6 mg/kg on postnatal day 12 (P12) or 10 mg/kg on P13 or 15 mg/kg on P15) or multiple doses (P12, P13, and P15) of NMDA. In prenatally MAM-exposed rats with single NMDA-provoked spasms at P15, we obtain the intracranial electroencephalography and examine the pretreatment response to adrenocorticotropic hormone (ACTH) or vigabatrin. Rat pups prenatally exposed to MAM exhibited a significantly greater number of spasms in response to single and multiple postnatal NMDA doses than vehicle-exposed controls. Vigabatrin treatment prior to a single NMDA dose on P15 significantly suppressed spasms in MAM group rats ( < 0.05), while ACTH did not. The MAM group also showed significantly higher fast oscillation (25-100 Hz) power during NMDA-induced spasms than controls ( = 0.047). This new model of MCD-based epileptic spasms with corresponding features of human spasms will be valuable for future research of the developmental epilepsy.
皮质发育畸形（MCDs）可导致儿童出现药物难治性癫痫和认知障碍。我们通过在产前用醋酸甲基氧化偶氮甲醇（MAM）处理大鼠以诱导皮质畸形，并在产后用N-甲基-D-天冬氨酸（NMDA）诱导痉挛，建立了一种与MCD相关的癫痫性痉挛新模型。为了使幼鼠产生皮质畸形，在妊娠第15天给怀孕大鼠腹腔注射两种剂量的MAM（15毫克/千克）。在产前暴露于MAM的大鼠和对照组中，通过单次（出生后第12天（P12）注射6毫克/千克或P13注射10毫克/千克或P15注射15毫克/千克）或多次剂量（P12、P13和P15）的NMDA引发痉挛。在产前暴露于MAM且在P15出现单次NMDA诱发痉挛的大鼠中，我们进行颅内脑电图检查，并检测对促肾上腺皮质激素（ACTH）或氨己烯酸的预处理反应。产前暴露于MAM的幼鼠对产后单次和多次NMDA剂量的反应中出现的痉挛次数明显多于暴露于赋形剂的对照组。在P15单次给予NMDA之前用氨己烯酸治疗可显著抑制MAM组大鼠的痉挛（P<0.05），而ACTH则无此作用。MAM组在NMDA诱导痉挛期间的快速振荡（25-100赫兹）功率也显著高于对照组（P=0.047）。这种具有人类痉挛相应特征的基于MCD的癫痫性痉挛新模型将对未来发育性癫痫的研究具有重要价值。
