Studies on valproate-induced perturbations of neurulation in the explanted chick embryo

The effect of the anticonvulsant sodium valproate on in vitro neurulation of the chick embryo, explanted after a 25-h in ovo incubation period, is described. Sodium valproate, at concentrations of 0.5-1.5 mM did not appear to have any profound effect on embryo growth when assessed by light microscopy. However scanning electron microscopy revealed a dose-dependent increase in the incidence of open anterior and posterior neuropores after 20 h of in vitro development (Stage 11). Concentrations of sodium valproate which were greater than 1.5 mM markedly increased the number of gross malformations, which were manifested as a complete disruption of the neural tube along its entire length. Failure of neuropore closure could not be attributed to a drug-induced neurodevelopmental delay as these defects were still apparent following 27 h of in vitro culture, a time coincident with the onset of embryo torsion.