AbstractThe antiepileptic drug Valproic acid (Val) is a known human teratogen. The risk is dose dependent and when the daily doses in pregnancy exceed 1400 mg up to 15% may be affected. The main clinical findings of the valproic acid congenital syndrome include lumbosacral meningomyelocele, intrauterin growth retardation, long forehead, flat nasal bridge, hypertelorisme, ephicanthal folds, long and smooth philtrum, narrow mouth with thin upper lip and rich under lip, small backwards rotated ears and overlapping toes. Many of the children will also suffer from developemental delay with reduced cognitive function, attention deficit disorder and learning difficulties. Rats exposed to Val in fetal life show abnormal cranial nerve nuclei, reduction in the number of cerebellar Purkinje cells and reduced size of the cerebellar hemisphere. The same histological changes were found in people with autism. It has therefore been proposed that the Val-exposed rat may serve as an animal model for autism. The aim of the present pilot study is to look for possible detrimental effects of Val exposure on the mitotic and apoptotic activity in immature granule neurones of the developing chick cerebellum.The chicken embryos were exposed to Val on embryonic day 16 (E16). Val was injected in four different concentrations (5mg/kg, 10mg/kg, 20mg/kg and 40mg/kg). The embryos were killed 24 hour later and the brains were fixed in paraforaldehyde. Coronary sections of the cerebellum were stained with H+E and PCNA and prepared for light microscopcal examination. The results show that compared with saline injected control embryos the Val exposed embryos demonstrated a dose-dependent increase in granule cell apoptosis in the cerebellum. There was also an increase in granule cell proliferation with higher doses of Val. These results indicate that developing chick cerebellum may be a suitable model system to study neurotoxic Val effects in fetal life.