Intracerebroventricular propofol is neuroprotective against transient global ischemia in rats: extracellular glutamate level is not a major determinant
T. Yano et al., Intracerebroventricular propofol is neuroprotective against transient global ischemia in rats: extracellular glutamate level is not a major determinant, BRAIN RES, 883(1), 2000, pp. 69-76
Excessive glutamate accumulation in extracellular space due to ischemia in
the central nervous system (CNS) is believed to initiate the cascade toward
irreversible neuronal damage. An intravenous general anesthetic, propofol
(2,6-diisopropylphenol) has been implicated to be neuroprotective against c
erebral ischemia. The purpose of this study was to test the hypothesis that
intracerebroventricular propofol produced a reduction in extracellular glu
tamate level during global ischemia and the resultant neuroprotection. Adul
t male Wistar rats were anesthetized with halothane in nitrous oxide/oxygen
and mechanically ventilated. Propofol (3 or 10 mg/kg), Intralipid(R) as a
vehicle for propofol, or artificial cerebrospinal fluid (aCSF) was administ
ered into the cerebral ventricles 15 min prior to a 10-min forebrain ischem
ia elicited by the four-vessel occlusion. Extracellular glutamate concentra
tion in the hippocampal CA1 was continuously monitored during the peri-isch
emic period with a microdialysis biosensor. Neuronal cell loss in the hippo
campal CA1 was evaluated by cresyl-violet staining of sections 7 days later
. Propofol (3 and 10 mg/kg) and Intralipid, compared with aCSF, similarly r
educed the extracellular glutamate accumulation during the peri-ischemic pe
riod (P<0.05), indicating that the extracellular glutamate reduction that w
as seen primarily reflects the effect of Intralipid. The number of intact n
eurons in the hippocampal CA1 in propofol 10 mg/kg-treated rats was signifi
cantly higher than that in rats treated with propofol 3 mg/kg, Intralipid,
or aCSF (P<0.05). We conclude that intracerebroventricular propofol exhibit
s neuroprotection against transient global forebrain ischemia; however, the
extracellular glutamate level during ischemia is not a major determinant o
f this neuroprotection. (C) 2000 Elsevier Science B.V. All rights reserved.