Audiogenic seizures and neuronal deficits following early exposure to barbiturate.
Sabra mice (n = 232) received phenobarbital (PhB) during the period of their prenatal development (PB group), or during the period of their neonatal development (NB group). PB mice received the barbiturate transplacentally by feeding their mothers PhB in their diet (3 g/kg food) on gestation days 9-18. NB mice received daily injections of PhB on postnatal days 2-21. On postnatal days 28-31 subjects were tested for their susceptibility to audiogenic seizures. Only 10% of the PB mice seized, a rate similar to the 13% of controls. However, the seizure rate of NB mice was three times higher than controls (37%, p less than 0.001). Sample groups were kept until day 50 and their brains removed and saved for quantitative histological analysis of the hippocampal neurons. In PB mice, there was only a small deficit in the number of the hippocampal pyramidal neurons compared to controls (15%, p less than 0.01), and no deficit in the granule cells. On the other hand, NB mice sustained a 35% deficit in the number of the pyramidal cells (p less than 0.001) and a 21% deficit in the granule cells (p less than 0.01). The sensitive period for the neuronal damage corresponded with the sensitive period for changes in seizures. Although other parts of the brain are also involved in seizure, the correlationi of the seizure with the hippocampus is important because the hippocampus is one of the major structures determining seizure.
D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001463:Barbiturates / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D010634:Phenobarbital / Q000378:metabolism / Q000633:toxicity; D011247:Pregnancy; D012640:Seizures / Q000209:etiology*
D001463:Barbiturates; D010634:Phenobarbital