Effects of Anticonvulsant Drugs on Chick Embryonic Neurons and Glia in Cell Culture

Abstract

The responses of neurons and glial cells to diphenylhydantoin (DPH), 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH) and phenobarbital were studied in cell cultures of dissociated chick embryo brain. Drugs were added to cultures daily for 3 days in concentrations ranging from 1 x 10^–4 to 1 x 10^–3M. Histological evaluations revealed that cultures treated with DPH exhibited fewer cell aggregates, fewer neurons and less prominent neuronal processes. Preliminary studies suggested that the degree of neurotoxicity might vary in different brain regions and at different stages of neural development. Cultures treated with HPPH exhibited toxicity similar to those treated with DPH but phenobarbital-treated cultures were not significantly different than control cultures. Incorporation of [¹⁴C]-leucine into protein was also decreased in cultures treated with DPH but not in those treated with phenobarbital.

Brain Maturation Following Administration of Phenobarbital, Phenytoin, and Sodium Valproate to Developing Rats or to Their Dams: Effects on Synthesis of Brain Myelin and Other Subcellular Membrane Proteins

“…Phenobarbital, however, appeared to be a relatively poor inhibitor. Culver and Vernadakis (1979), using neuronal cultures derived from chick brain at different stages of development, observed that [14C]leucine incorporation into pro-tein was decreased in the presence of phenytoin but not phenobarbital and confirms the observations of Swaiman and Stright (1973). Further, these authors also showed that phenytoin (but not phenobarbital) has a direct effect on the organization and development of brain cells and that neurons are particularly susceptible to the cytotoxic effects of phenytoin.…”

Effects of anticonvulsant drugs on brain cultures from chick embryos: A comparison with cultures from embryos treated in ovo

“…Even though morphological evaluation of glial cells has suggested an apparent lack of sensitivity to the toxic effects of anticonvulsant drugs [37], the biochemical results in our study have shown that glial cells were affected by the drugs. We found that phenytoin inhibited both CNP and CA activities in vivo, whereas valproate increased CNP activity both in vivo and in vitro.…”

Effect of Phenytoin on Human Cerebral Glucose Metabolism

“…Changes in glu cose metabolism and cognitive function may well be secondary manifestations of other biochemical effects of phenytoin. Phenytoin, for example, de creases cellular protein synthesis in a number of models of the developing nervous system (Swaiman and Stright, 1973;Jones and Woodbury, 1976;Culver and Vernadakis, 1979;Yanagihara and Hamberger, 1979). The most important effect of the drug appears to be on ionic fluxes across cellular and subcellular membranes (Woodbury, 1980).…”