Program of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University.
Laboratory for Pharmacotherapy and Experimental Neurology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University.
Biol Pharm Bull. 2023;46(9):1184-1193. doi: 10.1248/bpb.b23-00015.
Febrile seizures are seizures accompanied by a fever and frequently occur in children six months to five years of age. Febrile seizures are classified as simple or complex, and complex febrile seizures increase the risk of temporal lobe epilepsy after growth. Therefore, it is important to interfere with epileptogenesis after febrile seizures to prevent post-growth epilepsy. The present study challenged nutritional intervention using docosahexaenoic acid (DHA). Febrile seizures were induced in mice at the age of 10 d using a heat chamber, and seizure sensitivity was examined using pentylenetetrazol (PTZ) administration after growth. PTZ increased the seizure score and shortened the latency in the complex febrile seizure group compared to the control, hyperthermia and simple febrile seizure groups. Mice in the complex febrile seizure group showed abnormal electroencephalograms pre- and post-PTZ administration. Therefore, seizure susceptibility increases the episodes of complex febrile seizures. DHA supplementation after febrile seizures clearly suppressed the increased seizure susceptibility due to complex febrile seizures experienced in infancy. DHA also attenuated microglial activation after complex febrile seizures. Taken together, DHA suppressed microglial activation following complex febrile seizures, which may contribute to protecting the brain from post-growth seizures. The intake of DHA in infancy may protect children from high fever-induced developmental abnormalities.
热性惊厥是一种伴有发热的惊厥,常见于 6 个月至 5 岁的儿童。热性惊厥分为简单性或复杂性,复杂性热性惊厥会增加生长后颞叶癫痫的风险。因此,重要的是要在热性惊厥后干预癫痫发生,以预防生长后癫痫。本研究采用二十二碳六烯酸(DHA)进行营养干预挑战。在 10 天大的小鼠中使用热室诱导热性惊厥,并在生长后使用戊四氮(PTZ)给药检查惊厥敏感性。与对照组、高热和单纯热性惊厥组相比,复杂性热性惊厥组的 PTZ 增加了惊厥评分并缩短了潜伏期。复杂热性惊厥组的小鼠在给予 PTZ 前后出现异常脑电图。因此,惊厥易感性增加了复杂性热性惊厥的发作次数。热性惊厥后补充 DHA 可明显抑制因婴儿期经历的复杂性热性惊厥而引起的惊厥易感性增加。DHA 还可减轻复杂性热性惊厥后小胶质细胞的激活。总之,DHA 抑制了复杂性热性惊厥后的小胶质细胞激活,这可能有助于保护大脑免受生长后癫痫的影响。婴儿期摄入 DHA 可能会保护儿童免受高热引起的发育异常。