Behavioral evaluation of adult rats exposed in utero to maternal epileptic seizures

Abstract

We investigated the effects of exposure to maternal convulsive seizures in utero on the behavior of offspring. An epilepsy model was induced in female rats by administration of pilocarpine. Seizure frequency was evaluated for 60 days. The rats were then allowed to mate, and seizure frequency during pregnancy was recorded and compared with prepregnancy frequency. After birth, placentas of mothers were submitted for histopathological analysis. The behavior of the offspring was evaluated 3 months after birth. There was a decline in seizure frequency even though the placentas from epileptic mothers showed areas of ischemic infarction indicative of fetal hypoxia. Offspring of epileptic mothers manifested deficits in motor coordination in the rotarod test and increased immobility in the open-field test. No changes in anxiety and depression-like behaviors were observed. These results suggest that "in utero" exposure to maternal seizures can produce motor deficits in adult life, perhaps as a result of fetal hypoxia.

Social behavior impairment in offspring exposed to maternal seizures in utero

“…In agreement with these results, do Vale et al (2010) observed minimal anatomical changes in the hippocampus of offspring of epileptic dams, except the abnormal development of parvalbumin-positive interneurons. Interestingly, in our study, the frequency of seizures was higher during mid-gestation, corroborating previous findings by Lima et al (2010).…”

“…It has been suggested that seizures during pregnancy reduce the oxygen supply to the fetal circulation, which could affect intrauterine development. In fact, Lima et al (2010) observed areas of infarction in the placenta of females with epilepsy, suggesting the occurrence of low blood flow. Antenatal hypoxia-ischemia is one major cause of fetal brain damage, with long-term behavioral consequences (Dubovický 2010).…”

“…Along these lines, if a hypoxic-ischemic insult is one of the factors underlying seizures during pregnancy, which affects brain development, the frequency, duration and severity of seizures and gestational age of the fetus at the time of the insult must be considered. Although the studies of Raffo et al (2009), do Vale et al (2010 and Lima et al (2010) had recorded seizure frequency during pregnancy, the other parameters mentioned above were not evaluated, making comparisons difficult between the studies. The current results may explain Raffo et al's (2009) results, which did not find any changes in the development or behavior in offspring of epileptic mothers.…”

“…In brief, the authors showed a change in specific neuronal subpopulations; that is, the number of calbindinpositive interneurons was lower, and the number of parvalbumin-positive interneurons was higher in the experimental group when compared with the control group, suggesting that seizures during pregnancy affect the development of specific hippocampal interneurons in the offspring. Using the same animal model, Lima et al (2010) observed deficits in motor coordination in the rotarod test and increased immobility in the open-field test, with no changes in anxiety and depression-like behaviors. In addition, placentas from epileptic mothers showed areas of ischemic infarction, indicative of fetal hypoxia.…”

“…In both models, there was significant metabolic acidosis, 40% reduction in the levels of PO 2 , developmental delay and cerebral atrophy, which was mainly found in the cerebellum and hippocampus. Using an animal model of temporal lobe epilepsy developed by Turski et al (1983), do Vale et al (2010 investigated the effect of epileptic seizures during pregnancy on the hippocampal expression of calcium-binding proteins in the offspring. In brief, the authors showed a change in specific neuronal subpopulations; that is, the number of calbindinpositive interneurons was lower, and the number of parvalbumin-positive interneurons was higher in the experimental group when compared with the control group, suggesting that seizures during pregnancy affect the development of specific hippocampal interneurons in the offspring.…”