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

Objective 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. Method 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 χ2 test were used. Result 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 (χ2=13.817, P=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(F=0.312 and 0.257, P=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 P0(0 d after birth) and P84(84 d after birth) offspring from control and sham groups were normal, but neuronal damages were obvious in hippocampus of P0 and P84 offspring from kindling groups, and the damages in P0 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 3rd, 4th, and 5th days (F=6.276, 7.518, 18.422, P=0.030, 0.003, 0.000), significant less time in the target quadrant ((27±8) vs.(58±11)and(68±13)s, F=35.993, P=0.000) and reduced number of crossing the platform ((4.4±1.7) vs. (7.2±1.6) and (8.5±1.3)times, F=18.377, P=0.000). In addition, there was no significant difference between control and sham groups(P all >0.05). Conclusion 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. Key words: Epilepsy; Pregnancy; Cognition; Hippocampus; Offspring