Anesthetic concentrations of propofol protect against oxidative stress in primary astrocyte cultures: comparison with hypothermia.
BACKGROUND
The extracellular concentration of glutamate in the brain increases after oxidative damage. This increase may be caused, in part, by changes in glutamate transport by astrocytes. The authors hypothesized that propofol and hypothermia mitigate the effects on astrocytes of oxidative stress.


METHODS
Primary cultures of rat cerebral astrocytes were subjected to oxidative stress by incubation with tert-butyl hydroperoxide for 30 min, followed by a 30-90-min washout period. The effects of prophylactic (simultaneous with tert-butyl hydroperoxide application) and delayed (administered 30 min after the oxidant) propofol or hypothermia were determined by measuring the uptake of glutamate as well as the release of preloaded d-aspartate (a nonmetabolizable analog of glutamate) and endogenous lactate dehydrogenase (a cytosolic marker).


RESULTS
Delayed administration of an anesthetic concentration of propofol (1-3 microm) prevented the inhibition of high-affinity glutamate uptake, stimulation of d-aspartate release, and increase in lactate dehydrogenase release caused by tert-butyl hydroperoxide (1 mm, 37 degrees C). The protective effect of propofol (EC50 = 2 microm) on glutamate uptake was 20-fold more potent than that of alpha-tocopherol (EC50 = 40 microm). Prophylactic hypothermia (28 and 33 degrees C) also protected astrocytes from tert-butyl hydroperoxide. Delayed hypothermia was not protective but did not compromise rescue by propofol.


CONCLUSIONS
Clinical levels of propofol and hypothermia mitigate the effects of oxidative stress on astrocytic uptake and retention of glutamate, with propofol having a relatively larger therapeutic window. The ability of these treatments to normalize cell transport systems may attenuate the pathologic increase in extracellular glutamate at synapses and thus prevent excitotoxic neuronal death.
Peters
C E
CE
Department of Physiology, University of Western Ontario, London, Canada.
Korcok
J
J
Gelb
A W
AW
Wilson
J X
JX
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007036:Hypothermia, Induced; D018384:Oxidative Stress / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018686:Anesthetics, Intravenous; D018698:Glutamic Acid; D015742:Propofol