The influence of the timing of administration of thiopentone sodium on nitric oxide-mediated neurotoxicity in vitro.

Thiopentone sodium is a highly useful pharmacological agent that provides a neuroprotection against cerebral ischaemia. Since not all patients can receive thiopentone sodium before cerebral ischaemia occurs, we investigated the influence of timing of thiopentone sodium administration on the neurotoxicity induced by nitric oxide (NO) using Shibuta's established model of primary brain cultures. Cortical neurones prepared from 16-day gestational rat foetuses were used after 13-14 days in culture. The cells were exposed to an NO-donor, NOC-5 at 30 microM. Thiopentone sodium administered at 30 and 10 min before or 5, 10 and 15 min after exposure to NOC-5, but not thereafter, significantly attenuated NO-induced neurotoxicity compared with controls. The survival rate of the neurones in which thiopentone sodium was administered at 15 min after exposure to NOC-5 was 55.7+/-2.4%, compared to a 10.0+/-1.6% survival rate in neurones when thiopentone sodium was administered at 30 min after exposure to NOC-5. These findings demonstrate that thiopentone sodium, which protects cerebral cortical neurones against NO-mediated cytotoxicity, should be given as soon as possible in case ischaemic or hypoxic neuronal damage is predicted.