title: Thiopental sodium preserves the responsiveness to glutamate but not acetylcholine in rat primary cultured neurons exposed to hypoxia.
abstract: 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 2weeks 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 ([Ca(2+)]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 [Ca(2+)]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 [Ca(2+)]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.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: tmorita@anes.med.osaka-u.ac.jp.
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Morita
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: shibuta@anes.med.osaka-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shibuta
authors.affiliation: Center for Medical Science, International University of Health and Welfare, 2600-1 Kita-Kanemaru, Ohtawara, Tochigi 324-8501, Japan. Electronic address: junksk@iuhw.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Kosaka
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: fujino@anes.med.osaka-u.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Fujino
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology*; D000860:Hypoxia / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013874:Thiopental / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D018698:Glutamic Acid; D011189:Potassium Chloride; D013874:Thiopental; D000109:Acetylcholine; D002118:Calcium
keywords: Acetylcholine; Glutamic acid; Hypoxia; Neuron; Thiopental sodium