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.
Kelly
P G
PG
Department of Pharmacology, University College, Belfield, Dublin, Ireland.
Regan
C M
CM
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000254:growth & development; D008855:Microscopy, Electron, Scanning; D009436:Neural Tube Defects / Q000139:chemically induced* / Q000473:pathology; D014635:Valproic Acid / Q000633:toxicity*
D014635:Valproic Acid