Cultured neurons for testing antihypoxic drug effects

Cultured neurons of chick embryo cerebral hemispheres were used as an in vitro system for investigating the influence of several drugs on neuronal cell viability and metabolic activity under hypoxic conditions. Hypoxia was induced by addition of sodium cyanide to the nutrient medium, which led to a rapid depletion of energy stores. The ATP level of the cells and the protein content of the cultures were used to characterize the degree of neuronal damage after cytotoxic hypoxia and recovery, respectively, recovery lasting 15 min or 3 days. Various calcium antagonists, NMDA-antagonists, central depressants, central stimulants, nootropics, and miscellaneous drugs were tested. NMDA-antagonists and central depressants consistently protected the neurons against alterations caused by hypoxia. However, only one (flunarizine) out of five calcium antagonists, two (naftidrofuryl, pyritinol) out of 13 nootropics, the kappa-agonist ketazocine, and the ATPase inhibitor ouabaine exerted neuroprotection. The in vitro model seems to be suitable for testing neuroprotective drug effects and to be a valuable supplement for in vivo experiments, especially when the cellular mechanism of drug action has to be clarified.