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

• Published in: Journal of the neurological sciences Vol. 174; no. 1; pp. 9 - 15
• Main Authors: Shibuta, Satoshi, Kosaka, Jun, Inoue, Takaya, Shimizu, Tomoaki, Tomi, Katsuji, Mashimo, Takashi
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01-03-2000; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Cell Survival - drug effects; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - pathology; Drug Administration Schedule; Medical sciences; Neurons - drug effects; Neurons - pathology; Neuropharmacology; Neuroprotection; Neuroprotective agent; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Neurotoxins - antagonists & inhibitors; Neurotoxins - pharmacology; Nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - pharmacology; Nitric Oxide Donors - pharmacology; NOC-5; Pharmacology. Drug treatments; Primary cultured neurones; Rats; Rats, Wistar; Thiopental - administration & dosage; Thiopental - pharmacology; Thiopentone sodium; Timing; Triazenes - pharmacology; Neuroprotection; ONOO −, peroxynitrite anion; CMR, cerebral metabolic rate; Thiopentone sodium; O 2 −: superoxide anion; 5-FU, 5-fluoro-2′-deoxyuridine; PBS, phosphate buffered saline; NOS, nitric oxide synthase; SOD, superoxide dismutase; CNS, central nervous system; DMEM, Dulbecco’s modified Eagle’s minimum essential medium; FCS, foetal calf serum; NO, nitric oxide; Nitric oxide; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate; NOC-5, 1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene; SH, a sulfhydryl group; NOC-5; Timing; Primary cultured neurones; HS, horse serum; NMDA, N-methyl- d-aspartate; Cell culture; Cerebral cortex; Thiopental sodium; Rat; Rodentia; Central nervous system; Cytotoxicity; Neuroprotective agent; In vitro; Waiting time; Biological activity; Vertebrata; Mammalia; Neuron; Animal; Fetus; Barbiturates; Brain (vertebrata)
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/S0022-510X(99)00324-X

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 μM. 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.