Szot P, White S S, McCarthy E B, Turella A, Rejniak S X, Schwartzkroin P A
Geriatric Research, Education and Clinical Center (182B), VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108, USA.
Epilepsy Res. 2001 Sep;46(3):191-203. doi: 10.1016/s0920-1211(01)00285-6.
Seizure incidence varies significantly with age, with seizure susceptibility particularly high during the first few years of life. Of significant concern is what effects do brief, repetitive seizures have on the developing brain. We approached this issue by examining the change in seizure threshold, and related markers of neuronal activity and metabolic activity (c-fos mRNA and 2-deoxyglucose [2DG]), as a function of repetitive seizure episodes in immature and mature rats. Starting on postnatal day 15 (P15) (immature) or P60 (adult) rats were given two flurothyl seizures a day for 5 days (nine or ten seizures). The seizure latency profile, our measure of threshold, in immature versus adult rats across the 5-day testing period was different. In immature rats, threshold for the second seizure on each day was significantly lower than for the first seizure, suggesting that there was little refractoriness after the first seizure of the day. In contrast, the mature animal had a significantly longer threshold latency to the second seizure for the first 3 days of testing. The immature animal was also more likely than the adult to exhibit tonic extension as a feature of the first seizure of the day. Following repetitive seizures, more regions of the CNS showed c-fos mRNA expression in the immature animal than adults, suggesting that repetitive seizures in the immature animal activated a greater percentage of the brain. Compared with the effects of a single seizure, repetitive seizures resulted in less 2DG labeling in most regions of the brain (except the hippocampus); in the immature brain this difference was more distinct than in adults. The consequences of repetitive seizures in the immature animal results in distinctly different seizure behavior and neuronal activity pattern (c-fos expression) than that observed in the mature animal.
癫痫发作的发生率随年龄有显著差异，在生命的最初几年中癫痫易感性特别高。一个重要的问题是，短暂的重复性癫痫发作对发育中的大脑有什么影响。我们通过检查癫痫阈值的变化以及神经元活动和代谢活动的相关标志物（c-fos mRNA和2-脱氧葡萄糖[2DG]），来研究未成熟和成熟大鼠重复性癫痫发作的情况。从出生后第15天（P15，未成熟）或第60天（成年）开始，给大鼠每天进行两次氟代乙酰胺诱导的癫痫发作，持续5天（共九次或十次发作）。在5天的测试期内，未成熟大鼠与成年大鼠的癫痫发作潜伏期情况不同，我们将其作为阈值的衡量指标。在未成熟大鼠中，每天第二次癫痫发作的阈值明显低于第一次，这表明在当天第一次癫痫发作后几乎没有不应期。相比之下，在测试的前3天，成年动物第二次癫痫发作的阈值潜伏期明显更长。未成熟动物比成年动物更有可能在当天第一次癫痫发作时表现出强直性伸展。重复性癫痫发作后，未成熟动物中枢神经系统中显示c-fos mRNA表达的区域比成年动物更多，这表明未成熟动物的重复性癫痫发作激活了大脑中更大比例的区域。与单次癫痫发作的影响相比，重复性癫痫发作导致大脑大多数区域（除海马体外）的2DG标记减少；在未成熟大脑中，这种差异比成年大脑更为明显。未成熟动物重复性癫痫发作的后果导致其癫痫行为和神经元活动模式（c-fos表达）与成年动物明显不同。
