Neuronal overmaturation in dysraphism: ontogenic expression of neuropeptides in the fetal brain and developmental anomalies in exencephaly

Abstract

Starting from knowledge obtained in our previous studies of experimental dysraphism in chick embryos, the entity of neuronal over-growth observed in exencephaly was further investigated. The ontogenic expression of neuron-specific enolase (NSE), vasoactive intestinal polypeptide (VIP), and somatostatin was analyzed both in chick exencephaly of the natural product and in normal chick fetuses by carrying out immunohistochemical studies. In normal fetuses, immunostained elements positive for NSE first appeared in the spinal gray matter on postincubation day 16 and increased in intensity during the fetal period. By postnatal day 2, the cerebral peduncle, brain stem neurofibers, molecular layer of the cerebellum, corpus striatum, and piriform cortex became immunoreactive. No immunohistochemical reaction to VIP was observed during these stages. Somatostatin-positive elements were not identified during the fetal period, except in limited regions, such as the corpus striatum, which appeared to have weakly positive straining on day 21. The exencephalic fetuses, however, demonstrated extremely advanced neuronal maturation, with intense immunoreactivity already being manifest in various regions, including the corpus striatum, piriform cortex, spinal gray matter, and brain stem nuclei, on day 16 of the fetal period. Somatostatin-positive elements also appeared at this stage in chick exencephaly, but such immunoreactivity was localized, particularly in the overgrown foci. The present study showed that the neuronal maturation process in some neurons of exencephalic brain and spinal cord was definitely further advanced than that in normal controls. A possible clinical application of NSE and somatostatin measurement as markers for dysraphic states in the fetus is suggested.