Wirrell E C, Armstrong E A, Osman L D, Yager J Y
Division of Neurosciences, Department of Pediatrics, University of Saskatchewan, Royal University Hospital, Saskatoon, Saskatchewan S7N 0W8, Canada.
Pediatr Res. 2001 Oct;50(4):445-54. doi: 10.1203/00006450-200110000-00005.
This study was undertaken to clarify whether seizures in the newborn cause damage to the healthy brain and, more specifically, to determine the extent to which seizures may contribute to the brain-damaging effects of hypoxia-ischemia (HI). Seizures were induced in 10-d-old rat pups with kainic acid (KA). Seizure duration was determined electrographically. HI was induced by common carotid artery ligation followed by exposure to 8% oxygen for either 15 or 30 min. Six groups of animals were assessed: 1) controls [neither KA nor HI (group I)]; 2) group II, KA alone; 3) group III, 15 min HI alone; 4) group IV,15 min HI plus KA; 5) group V, 30 min HI alone; and 6) group VI, 30 min HI plus KA. Animals were assessed neuropathologically at 3 (early) and 20 (late) d of recovery. KA injection without hypoxia resulted in continuous clinical and electrographic seizures lasting a mean of 282 min. No neuropathologic injury was seen in groups I (no HI or KA), II (KA alone), III (15 min HI alone), or IV (15 min HI and KA). Animals in group V (30 min HI alone) displayed brain damage with a mean score of 2.3 and 0.60 at 3 and 20 d of recovery, respectively. Animals in group VI (30 min HI and KA) had a mean score of 12.1 and 3.65 at 3 and 20 d of recovery, respectively. Compared with group V, the increased damage as a result of the seizure activity in group VI occurred exclusively in the hippocampus. Status epilepticus in the otherwise "healthy" neonatal brain does not cause neuropathologic injury. However, seizures superimposed on HI significantly exacerbate brain injury in a topographically specific manner.
本研究旨在阐明新生儿癫痫发作是否会对健康大脑造成损害，更具体地说，是要确定癫痫发作在多大程度上可能导致缺氧缺血（HI）对大脑的损害作用。用 kainic 酸（KA）诱导 10 日龄大鼠幼崽发生癫痫发作。通过脑电图确定癫痫发作持续时间。通过结扎颈总动脉并使其暴露于 8%氧气中 15 或 30 分钟来诱导 HI。评估了六组动物：1）对照组[既无 KA 也无 HI（I 组）]；2）II 组，仅 KA；3）III 组，仅 15 分钟 HI；4）IV 组，15 分钟 HI 加 KA；5）V 组，仅 30 分钟 HI；6）VI 组，30 分钟 HI 加 KA。在恢复的第 3 天（早期）和第 20 天（晚期）对动物进行神经病理学评估。无缺氧情况下注射 KA 导致持续的临床和脑电图癫痫发作，平均持续 282 分钟。在 I 组（无 HI 或 KA）、II 组（仅 KA）、III 组（仅 15 分钟 HI）或 IV 组（15 分钟 HI 和 KA）中未观察到神经病理学损伤。V 组（仅 30 分钟 HI）的动物在恢复的第 3 天和第 20 天分别显示出平均评分为 2.3 和 0.60 的脑损伤。VI 组（30 分钟 HI 和 KA）的动物在恢复的第 3 天和第 20 天的平均评分分别为 12.1 和 3.65。与 V 组相比，VI 组因癫痫发作活动导致的损伤增加仅发生在海马体中。原本“健康”的新生儿大脑中的癫痫持续状态不会导致神经病理学损伤。然而，叠加在 HI 上的癫痫发作会以地形学上特定的方式显著加重脑损伤。
