Thiopental sodium preserves the responsiveness to glutamate but not acetylcholine in rat primary cultured neurons exposed to hypoxia

Although many in vitro studies demonstrated that thiopental sodium (TPS) is a promising neuroprotective agent, clinical attempts to use TPS showed mainly unsatisfactory results. We investigated the neuroprotective effects of TPS against hypoxic insults (HI), and the responses of the neurons to l-glutamate and acetylcholine application. Neurons prepared from E17 Wistar rats were used after 2 weeks in culture. The neurons were exposed to 12-h HI with or without TPS. HI-induced neurotoxicity was evaluated morphologically. Moreover, we investigated the dynamics of the free intracellular calcium ([Ca2+]i) in the surviving neurons after HI with or without TPS pretreatment following the application of neurotransmitters. TPS was neuroprotective against HI according to the morphological examinations (0.73 ± 0.06 vs. 0.52 ± 0.07, P = 0.04). While the response to l-glutamate was maintained (0.89 ± 0.08 vs. 1.02 ± 0.09, P = 0.60), the [Ca2+]i response to acetylcholine was notably impaired (0.59 ± 0.02 vs. 0.94 ± 0.04, P < 0.01). Though TPS to cortical cultures was neuroprotective against HI morphologically, the [Ca2+]i response not to l-glutamate but to acetylcholine was impaired. This may partially explain the inconsistent results regarding the neuroprotective effects of TPS between experimental studies and clinical settings.