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 rec eive thiopentone sodium before cerebral ischaemia occurs, we investigated t he influence of timing of thiopentone sodium administration on the neurotox icity induced by nitric oxide (NO) using Shibuta's established model of pri mary 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 mu M. 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 administ ered 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 a t 30 min after exposure to NOC-5. These findings demonstrate that thiopento ne sodium, which protects cerebral cortical neurones against NO-mediated cy totoxicity, should be given as soon as possible in case ischaemic or hypoxi c neuronal damage is predicted. (C) 2000 Elsevier Science BV. All rights re served.