Reduced seizure threshold and hippocampal cell loss in rats exposed to alcohol during the brain growth spurt
Reduced seizure threshold and hippocampal cell loss in rats exposed to alcohol during the brain growth spurt
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DOI：
10.1111/j.1530-0277.2001.tb02129.x
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发表时间：
2001-01-01
影响因子：
3.2
通讯作者：
Lothman, EW
中科院分区：
文献类型：
--
作者：
Bonthius, DJ;Woodhouse, J;Lothman, EW
背景：癫痫是胎儿酒精综合征（FAS）患儿神经功能障碍的一个显著体征。然而，尚不清楚这些儿童的癫痫障碍是否直接归因于酒精的神经致畸作用或伴随母亲酒精中毒的其他因素。海马体易受酒精诱导的病理变化的影响，海马体的功能障碍常常表现为癫痫。我们研究了酒精暴露在开发过程中的癫痫发作阈值的影响，并检查癫痫发作阈值和酒精诱导的神经元损失从hippocamps.Methods：大鼠幼崽接受0.85，2.5，或3.75克/公斤的酒精通过胃内插管每天在产后天（PD）4-9之间的关系。还包括插管对照组和插管对照组。为了评估一天酒精暴露的影响，另一组接受3.75 g/kg酒精单独PD 4。在PD 31或PD 90时，通过静脉输注促惊厥剂戊四唑（PTZ）测定行为癫痫发作阈值。此外，通过记录齿状回的细胞外场电位来确定电图癫痫发作阈值。海马CA 1区锥体细胞，CA 3区锥体细胞，齿状回颗粒细胞的数量测定体视学。结果：每日暴露于酒精导致剂量依赖性降低癫痫发作阈值和选择性损失的CA 1区锥体细胞。癫痫发作阈值的降低与CA 1锥体细胞的丢失显著相关。细胞外场电位的记录证实了酒精诱导的癫痫发作阈值的降低，证明了PTZ诱导的癫痫发作涉及海马-海马旁回路，并提供了海马结构是酒精暴露动物中PTZ诱导癫痫发作的发生器的证据。这些发现表明，发育中的大脑暴露在酒精中可以永久性地降低行为和电图的阈值。能选择性杀伤海马CA 1区锥体细胞。病理结果和生理记录都支持这样的概念，即酒精暴露的动物癫痫发作阈值降低是由于海马病理学。
Background: Epilepsy is a prominent sign of neurologic dysfunction in some children with fetal alcohol syndrome (FAS). However, it is unknown whether the epileptic disorders in these children are directly due to the neuroteratogenic effects of alcohol or to some other factor accompanying maternal alcoholism. The hippocampus is vulnerable to alcohol-induced pathologic changes, and dysfunction of the hippocampus often manifests as epilepsy. We examined the effect of alcohol exposure during development on the seizure threshold and examined the relationship between alteration of seizure threshold and alcohol-induced neuronal loss from the hippocampus.Methods: Rat pups received 0.85, 2.5, or 3.75 g/kg of alcohol via intragastric intubation daily over postnatal days (PD) 4-9. An intubated control and a suckle control group were also included. To assess the effect of a single day of alcohol exposure, an additional group received 3.75 g/kg of alcohol on PD 4 alone. Behavioral seizure thresholds were determined by intravenous infusion of the proconvulsant, pentylenetetrazol (PTZ), on PD 31 or on PD 90. In addition, electrographic seizure thresholds were determined by recording extracellular field potentials from the dentate gyrus. The number of hippocampal CA1 pyramidal cells, CA3 pyramidal cells, and granule cells of the dentate gyrus were determined by stereology.Results: Daily exposure to alcohol resulted in a dose-dependent decrease in the seizure threshold and in the selective loss of CA1 pyramidal cells. Reduction in the seizure threshold was significantly correlated with loss of CA1 pyramidal cells. Recordings of extracellular field potentials confirmed the alcohol-induced reduction in seizure threshold, demonstrated that PTZ-induced seizures involve hippocampal-parahippocampal circuitry, and provided evidence that the hippocampal formation is the generator of the PTZ-induced seizures in alcohol-exposed animals.Conclusions: These findings demonstrate that exposure of the developing brain to alcohol can permanently reduce the threshold for both behavioral and electrographic seizures and can selectively kill hippocampal CA1 pyramidal cells. Both the pathologic findings and the physiologic recordings support the concept that the reduced seizure threshold in alcohol-exposed animals is due to hippocampal pathology.