High-dose propofol triggers short-term neuroprotection and long-term neurodegeneration in primary neuronal cultures from rat embryos.
This study investigated the effects of propofol on primary neuronal cultures from rat embryos. Primary cortical neuronal cultures were prepared from Wistar rat embryos (E18). The viability of cells exposed to 0.01, 0.1 or 1 mg/ml propofol for up to 48 h was assessed using a methyltetrazolium assay. In order to evaluate the role of gamma-aminobutyric acid-A (GABA(A)) receptors, cells were also preincubated with the GABA(A)-receptor antagonists, gabazine and picrotoxin. Propofol at a concentration of 1 mg/ml significantly reduced cell viability after 12 h. In contrast, this concentration led to a significant increase in cell viability at 3 and 6 h. The GABA(A)-receptor antagonists did not influence the neurodegenerative effect of propofol but abolished its neuroprotective effect. DNA fragmentation as a marker of apoptosis was elevated after 24 h propofol treatment. These results confirm that high doses of propofol can cause GABA(A) receptor triggered neuroprotection and a subsequent time-dependent, but GABA(A) independent, neurodegeneration in primary cortical neurons.
Berns
M
M
Department of Neonatology, Charité Centre 17 for Gynaecology, Perinatal, Paediatric and Adolescent Medicine with Perinatal Centre and Human Genetics, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany. monika.berns@charite.de
Seeberg
L
L
Schmidt
M
M
Kerner
T
T
D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology*; D058787:GABA-A Receptor Antagonists; D009410:Nerve Degeneration / Q000473:pathology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D015742:Propofol / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D058787:GABA-A Receptor Antagonists; D018696:Neuroprotective Agents; D015742:Propofol