A strong epileptogenic effect of mechanical injury can be reduced in the dysplastic rat brain. Long-term consequences of early prenatal gamma-irradiation

Abstract

An exposure of rats to gamma-radiation at different stages of prenatal development produces brain dysplasias of different degree displaying also different susceptibility to pilocarpine-induced seizures. Following irradiation on prenatal day 13 (E13), the susceptibility is minimal and significantly lower even in relation to non-irradiated rats [Setkowicz, Z., Janeczko, K., 2003. Long-term changes in susceptibility to pilocarpine-induced status epilepticus following neocortical injuries in the rat at different developmental stages. Epilepsy Res. 53, 216-224]. On the other hand, the rat brain injured on postnatal day 30 presents very high susceptibility to seizures in the same pilocarpine model of epilepsy [Setkowicz, Z., Kluk, K., Janeczko, K., 2003. Long-term changes in postnatal susceptibility to pilocarpine-induced seizures in rats exposed to gamma radiation at different stages of prenatal development. Epilepsia 44, 1267-1273]. It could, therefore, be hypothesised that the congenital brain dysplasia produced by irradiation on E13 would minimize the highly increased susceptibility to seizures observed in the injured brain. Wistar rats were exposed to gamma-rays on E13 and they received a mechanical brain injury on postnatal day 30 (P30). On postnatal day 60, pilocarpine was injected to evoke status epilepticus. During a 6-h period following the injection, motor manifestations of seizure activity were recorded and rated. Seven days after pilocarpine injection, the animals were sacrificed and their brains were fixed. Pilocarpine injections in non-irradiated rats with brains injured on P30 evoked seizures of very high intensity and extremely high mortality in relation to non-injured controls. This high susceptibility to seizures following the brain injury was considerably decreased in rats irradiated on E13. The data provide evidence that the brain dysplasia in the rat acquired at this stage of prenatal development can significantly reduce the increased susceptibility to seizures evoked by the postnatal brain injury.