Intracerebroventricular propofol is neuroprotective against transient global ischemia in rats: extracellular glutamate level is not a major determinant

Citation
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
Citations number
46
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BRAIN RESEARCH
ISSN journal
00068993 → ACNP
Volume
883
Issue
1
Year of publication
2000
Pages
69 - 76
Database
ISI
SICI code
0006-8993(20001110)883:1<69:IPINAT>2.0.ZU;2-W
Abstract
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.