title: An assessment of the cerebroprotective potential of volatile anaesthetics using two independent methods in an in vitro model of cerebral ischaemia.
abstract: Previous studies using a rat brain slice model of cerebral 'ischaemia' (hypoxia and hypoglycaemia) have suggested that volatile anaesthetics may have cerebroprotective potential. In this study, we tested the cerebroprotective profile of four volatile anaesthetics in this model by two independent means: voltammetric measurement of 'ischaemia'-induced dopamine (DA) release and post-'ischaemic' tissue staining with 2,3,5-triphenyltetrazolium chloride (TTC). 'Ischaemia' caused a characteristic pattern of DA release. Halothane, isoflurane and enflurane did not affect the time from onset of 'ischaemia' to the initiation of DA release. However, all three volatile agents significantly increased (P<0.01, P<0.05, P<0.001, respectively) the time taken for 'ischaemia'-induced DA release to reach maximum and reduced the rate of DA release. Enflurane, unlike halothane or isoflurane, reduced the maximal extracellular DA concentration induced by 'ischaemia' (P<0.01). The effects of sevoflurane were inconsistent. At the higher concentrations used, the volatile anaesthetics frequently changed the character of DA release from monophasic to biphasic, an effect only previously seen in this model with Na(+) channel blockers. 'Ischaemia' also diminished the subsequent level of tissue staining with TTC. When the effects of the volatile agents were analysed by TTC staining, only enflurane showed any cerebroprotective effects and these were limited to the striatum (P<0.01). High concentrations of halothane, isoflurane and enflurane appeared to have some 'toxic' effects, reducing TTC staining in control slices. In summary, we do not find any consistent evidence that volatile anaesthetics are cerebroprotective in this model.
authors.affiliation: Neurotransmission Laboratory, Academic Department of Anaesthesia and Intensive Care, Barts and the London School of Medicine and Dentistry, Alexandra Wing, Royal London Hospital, Whitechapel, London E1 1BB, UK.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Toner
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Milne
authors.forename: Karen L
authors.initials: KL
authors.lastname: Blatchford
authors.forename: Daniel P
authors.initials: DP
authors.lastname: McLaughlin
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Stamford
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018685:Anesthetics, Inhalation; D018696:Neuroprotective Agents; D004298:Dopamine