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[产前母体癫痫发作对仔鼠海马损伤及认知缺陷的影响]

[Effects of prenatal maternal seizure on hippocampal damage and cognitive deficits in offspring rats].

作者信息

Lu Y, Wang W P, Wang X X, Feng J J, Guo Z P, Liu L M, Xie T, Zhao R R, Cai Y L

机构信息

*Department of Pediatrics, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.

出版信息

Zhonghua Er Ke Za Zhi. 2016 Oct 2;54(10):746-751. doi: 10.3760/cma.j.issn.0578-1310.2016.10.007.

Abstract

To observe hippocampal damage and cognitive impairment of offspring exposed to prenatal maternal seizure induced by amygdala kindling, and to explore the underlying mechanism by the detection of pathological changes of placenta. Adult female SD rats were randomly divided into three groups: control group(8 rats), kindling group(12 rats) and sham group(8 rats). All the rats were allowed to mate after one week's fully kindling. The pregnant rats in kindling group received electric stimulation every 48 h. Dams were allowed to deliver naturally. Effects of maternal seizure on the number of offspring, the survival rate and body weight of pups were observed. HE staining was used to visualize histopathological changes of placenta. Morris water maze test was used to assess the cognitive function and Nissal's staining to detect hippocampal morphology of the offspring. One-way ANOVA analysis and χ test were used. Compared with the sham group (95%(78/82)) and the control group (95%(82/86)), the survival rate of pups in kindling group(81%(66/82))was much lower (χ=13.817, =0.001). There were no significant differences in the number of pups per litter and pups birth-weight between kindling group and sham group or control group(=0.312 and 0.257, =0.736 and 0.776). HE staining showed that placental tissues from control and sham groups were normal whereas the histologic abnormalities of placentas from kindling group were characterized by thickening of the villus vascular walls, luminal stenosis, trophoblasts hyperplasia, abnormalities of trophoblasts with nuclear pyknosis and karyorrhexis and accumulation of inflammatory lymphocytes in labyrinthine zone. Nissl staining showed that neurons in hippocampus of P(0 d after birth) and P(84 d after birth) offspring from control and sham groups were normal, but neuronal damages were obvious in hippocampus of P and P offspring from kindling groups, and the damages in P pups were severe with a marked loss of neuron, shrinkage of cells and nuclear pyknosis and karyorrhexis. In the Morris water maze, compared with the sham group ((29±8), (19±9), (10±4)s) and the control group ((25±6), (17±5), (14±4)s) rats in the kindling group ((36±8), (29±8), (30±11)s) exhibited significantly longer escape latency from the 3 4 and 5 days (=6.276, 7.518, 18.422, =0.030, 0.003, 0.000), significant less time in the target quadrant ((27±8) .(58±11)and(68±13)s, =35.993, =0.000) and reduced number of crossing the platform ((4.4±1.7) . (7.2±1.6) and (8.5±1.3)times, =18.377, =0.000). In addition, there was no significant difference between control and sham groups( all >0.05). The prenatal maternal seizures induced significant pathological damages to hippocampus and cognitive impairment of offspring. Hypoxia-ischemia of placenta might play an important role in this process.

摘要

观察产前母鼠杏仁核点燃诱导癫痫发作对子代海马损伤及认知功能障碍的影响,并通过检测胎盘病理变化探讨其潜在机制。将成年雌性SD大鼠随机分为三组:对照组(8只)、点燃组(12只)和假手术组(8只)。所有大鼠在充分点燃1周后进行交配。点燃组孕鼠每48小时接受一次电刺激。母鼠自然分娩。观察母鼠癫痫发作对子代数量、幼崽存活率和体重的影响。采用HE染色观察胎盘组织病理学变化。采用Morris水迷宫试验评估子代认知功能,尼氏染色检测子代海马形态。采用单因素方差分析和χ检验。与假手术组(95%(78/82))和对照组(95%(82/86))相比,点燃组幼崽存活率(81%(66/82))显著降低(χ=13.817,P=0.001)。点燃组与假手术组或对照组每窝幼崽数量和幼崽出生体重差异均无统计学意义(P=0.312和0.257,P=0.736和0.776)。HE染色显示,对照组和假手术组胎盘组织正常,而点燃组胎盘组织学异常表现为绒毛血管壁增厚、管腔狭窄、滋养层细胞增生、滋养层细胞异常伴核固缩和核碎裂以及迷路区炎性淋巴细胞聚集。尼氏染色显示,对照组和假手术组出生后0天(P0)和出生后84天(P84)子代海马神经元正常,但点燃组P0和P84子代海马神经元损伤明显,P0幼崽损伤严重,神经元明显丢失、细胞萎缩、核固缩和核碎裂。在Morris水迷宫试验中,与假手术组((29±8)、(19±9)、(10±4)秒)和对照组((25±6)、(17±5)、(14±4)秒)相比,点燃组大鼠在第3、4和5天的逃避潜伏期显著延长(F=6.276、7.518、18.422,P=0.030、0.003、0.000),在目标象限的时间显著减少((27±8)、(58±11)和(68±13)秒,F=35.993,P=0.000),穿越平台的次数减少((4.4±1.7)、(7.2±1.6)和(8.5±1.3)次,F=18.377,P=0.000)。此外,对照组和假手术组之间差异无统计学意义(均P>0.05)。产前母鼠癫痫发作可导致子代海马显著的病理损伤和认知功能障碍。胎盘缺氧缺血可能在此过程中起重要作用。

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