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目的探讨新生期大鼠反复痫性发作后的形态学,行为学以及糖皮质激素水平的变化。方法64只出生后一天的Wistar大鼠随机分为惊厥组40只和对照组24只。惊厥组的新生鼠在出生后1天(P1)、4天(P4)、7天(P7)给予腹腔注射匹罗卡品,制备新生鼠癫痫模型;对照组的新生鼠腹腔注射生理盐水。惊厥组分别在第 3次致痫后在即刻(Ⅰ组)、第4 天(Ⅱ组)、第14 天(Ⅲ组)、第42天(Ⅳ组)四个时间点处死,各时间点设相应对照组,处死前36 h惊厥组和对照组的大鼠腹腔注射BrdU。所有大鼠处死前均取血检测糖皮质激素。第Ⅳ组从P40开始进行Morris水迷宫试验。结果新生鼠3次发作后即刻和第4天与相应日龄对照组相比,齿状回BrdU阳性细胞数明显减少(P<0.05),而癫痫发作后14天和42天BrdU阳性细胞数增加,但发作后14天差异无统计学意义(P>0.05)。在4天的Morris水迷宫试验中,匹罗卡品处理组大鼠到达平台的时间均长于对照组,但是只有第1天和第2天有统计学意义(P<0.05)。检测结果表明高水平的糖皮质激素一直持续到发作后第4天,糖皮质激素水平与BrdU阳性细胞数呈负相关。结论新生大鼠反复痫性发作会造成早期神经发生减少,而后期神经发生增加;造成大鼠成年后认知功能缺陷;造成糖皮质激素水平增高,这与痫性大鼠形态学和行为学方面的改变有关。
Objective To investigate the changes of morphological, behavioral and glucocorticoid levels in neonatal rats after repeated epileptic seizures. Methods Sixty-four Wistar rats were randomly divided into convulsion group (n = 40) and control group (n = 24). Neonatal rats in the convulsion group were injected intraperitoneally with pilocarpine 1 day after birth (P1), 4 days (P4), and 7 days (P7) to prepare a neonatal rat model of epilepsy. Neonatal rats in the control group were injected intraperitoneally with saline. The convulsion group was sacrificed at the four time points immediately after the third epilepsy (group Ⅰ), the fourth day (group Ⅱ), the fourteenth day (group Ⅲ) and the day 42 (group Ⅳ) The corresponding control group, 36 h before sacrifice convulsion group and control group of rats intraperitoneal injection of BrdU. All rats were sacrificed before the blood test glucocorticoid. Group IV began Morris water maze test from P40. Results BrdU positive cells in the dentate gyrus decreased significantly (P <0.05) immediately after the third attack and on the fourth day in the newborn rats compared with the corresponding control group, while the number of BrdU positive cells increased 14 days and 42 days after the onset of seizures , But there was no significant difference 14 days after the onset of attack (P> 0.05). In the 4-day Morris water maze test, rats on the pilocarpine-treated group reached the plateau longer than the control group, but only on day 1 and day 2 (P <0.05). The results showed that high levels of glucocorticoids continued until the fourth day after the onset of glucocorticoid levels and BrdU positive cells was negatively correlated. Conclusions The recurrent seizures in neonatal rats may lead to the decrease of early neurogenesis and the later increase of neurogenesis, which may cause cognitive deficits in adult rats and increase the level of glucocorticoid, which is related to the morphological and behavioral aspects of epileptic rats Related to the change.