The GABAergic system of the developing neocortex has a reduced capacity to recover from in utero injury in experimental cortical dysplasia

Abstract

Cortical dysplasia is frequently associated with epilepsy but mechanisms underlying this association are poorly understood. Rats irradiated in utero serve as an injury-based model of cortical dysplasia. Prior studies in mature rats have shown a selective reduction in the number of neocortical interneurons after in utero irradiation. This study attempted to clarify the nature of the radiation injury to the developing neocortical GABAergic system after exposure to γ-irradiation on the 17th day of gestation (E17). Stereological methods were used to quantify absolute numbers of total neurons (TN) and GABAergic neurons in the neocortex on E21 and postnatal day 6 (P6). In irradiated rats, TN was decreased to about 50% of controls at both time points. However, TN doubled between the 2 time points, even in irradiated animals. In controls, GABAergic neurons increased 10-fold between E21 and P6, but there was no difference in GABAergic counts between the 2 time points in irradiated animals. This led to a dramatic reduction in the percentage of neocortical neurons that were GABAergic in irradiated animals at P6 (9% vs 18%). This study shows that, in contrast to non-GABAergic neurons, the neocortical GABAergic system has a limited capacity to recover from radiation-induced in utero injury.