Differential neurotoxic effects of propofol on dissociated cortical cells and organotypic hippocampal cultures.
BACKGROUND
Propofol is a widely used anesthetic agent for adults and children. Although extensive clinical use has demonstrated its safety, neurologic dysfunctions have been described after the use of this agent. A recent study on a model of aggregating cell cultures reported that propofol might cause irreversible lesions of gamma-aminobutyric acid-mediated (GABAergic) neurons when administered at a critical phase of brain development. We investigated this issue by comparing the effects of long-term propofol treatment on two models of brain cultures: dissociated neonatal cortical cell cultures and organotypic slice cultures.


METHODS
Survival of GABAergic neurons in dissociated cultures of newborn rat cortex (postnatal age, 1 day) treated for 3 days with different concentrations of propofol was assessed using histologic and cytochemical methods. For hippocampal organotypic slice cultures (postnatal age, 1 and 7 days), cell survival was assessed by measuring functional and morphologic parameters: extracellular and intracellular electrophysiology, propidium staining of dying cells, and light and electron microscopy.


RESULTS
In dissociated neonatal cell cultures, propofol induced dose-dependent lesions of GABAergic neurons and of glial cells. In contrast, no evidence for neurotoxic effects of propofol were found after long-term treatment of organotypic slice cultures. Excitatory transmission was not affected by propofol, and inhibitory transmission was still functional. Histologic preparations showed no evidence for cell degeneration or death.


CONCLUSIONS
Although long-term applications of propofol to dissociated cortical cell cultures produced degeneration and death of GABAergic neurons and glial cells, no such lesions were found when using a model of postnatal organotypic slice cultures. This conclusion is based on both functional and morphologic tests.
Spahr-Schopfer
I
I
Department of Anesthesiology, University Medical Center, University Hospital of Geneva, Geneva, Switzerland. Isabelle.SpahrSchopfer@hcuge.ch
Vutskits
L
L
Toni
N
N
Buchs
P A
PA
Parisi
L
L
Muller
D
D
D018686:Anesthetics, Intravenous / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015742:Propofol / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects
D018686:Anesthetics, Intravenous; D011963:Receptors, GABA-A; D015742:Propofol