Effects of sevoflurane on dopamine, glutamate and aspartate release in an in vitro model of cerebral ischaemia

Abstract

Release of excitatory amino acids and dopamine plays a central role in neuronal damage after cerebral ischaemia. In the present study, we used an in vitro model of ischaemia to investigate the effects of sevoflurane on dopamine, glutamate and aspartate efflux from rat corticostriatal slices. Slices were superfused with artificial cerebrospinal fluid at 34 degrees C and episodes of 'ischaemia' were mimicked by removal of oxygen and reduction in glucose concentration from 4 to 2 mmol litre(-1) for < or = 30 min. Dopamine efflux was monitored in situ by voltammetry while glutamate and aspartate concentrations in samples of the superfusate were measured by HPLC with fluorescence detection. Neurotransmitter outflow from slices was measured in the absence or presence of sevoflurane (4%). After induction of ischaemia in control slices, there was a mean (SEM) delay of 166 (7) s (n = 5) before sudden efflux of dopamine which reached a maximum extracellular concentration of 77.0 (15.2) micromol litre(-1). Sevoflurane (4%) reduced the rate of dopamine efflux during ischaemia (6.90 (1.5) and 4.73 (1.76) micromol litre(-1) s(-1) in controls and sevoflurane-treated slices, respectively; P<0.05), without affecting its onset or magnitude. Excitatory amino acid efflux was much slower. lschaemia-induced glutamate efflux had not reached maximum after 30 min of ischaemia. Basal (pre-ischaemic) glutamate and aspartate efflux per slice was 94.8 (24.8) and 69.3 (31.5) nmol litre(-1) superfusate (n = 4) and was not significantly reduced by 4% sevoflurane. lschaemia greatly increased glutamate and aspartate efflux (to a maximum of 919 (244)% and 974 (489)% of control, respectively). However, ischaemia-induced efflux of both glutamate and aspartate was significantly reduced by 4% sevoflurane (P < 0.001 for glutamate, P < 0.01 for aspartate). In summary, sevoflurane may owe part of its reported neuroprotective effect to a reduction of ischaemia-induced efflux of excitatory amino acids and, to a lesser extent, dopamine.

Inhalational Anesthetics as Neuroprotectants or Chemical Preconditioning Agents in Ischemic Brain

“…In addition, protection has been shown when sevoflurane is applied to rat corticostriatal brain slices treated with OGD (Toner et al, 2001). Short-(72 to 96 h) and longterm (28 days) neuroprotection in rats after ischemic insult has also been shown (Pape et al, 2006;Warner et al, 1993;Werner et al, 1995).…”

Sevoflurane depolarizes pre‐synaptic mitochondria in the central nervous system

“…VA possess neuroprotective properties in both in vivo and in vitro animal models of ischemia (99,100). One possible mechanism would be their ability to reduce neuronal excitability through enhanced inhibitory and depressed excitatory synaptic transmission (101)(102)(103).…”

Endogenous Dopamine Amplifies Ischemic Long-Term Potentiation via D1 Receptors

“…It is well known, in fact, that a massive release of dopamine occurs during ischemic events in the striatum and that endogenous dopamine amplifies the neuronal damage caused by excitotoxicity and energy deprivation. [13][14][15][16] Endogenous dopamine, however, can facilitate both acute necrotic and delayed apoptotic neuronal death by additional mechanisms, such as the control of intracellular calcium levels and the production of free radicals. 43,44 The ischemia-induced abnormal release of endogenous dopamine in vulnerable brain areas, such as striatum, cerebral cortex, and hippocampus, may represent the critical factor that transforms a transient ischemic attack into an ischemic episode causing irreversible consequences for brain tissue and synaptic circuits.…”

“…10 -12 Ischemia also causes a large increase in dopamine levels in the striatum, 13 and considerable evidence supports the idea that monoamines or their metabolic by-products may become neurotoxic during metabolic impairment, either directly or from interplay with the glutamatergic system. 14,15 In an in vitro model of striatal ischemia, for example, reduction of dopamine release has been found to be associated with a better histological outcome, 13 and unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra has been reported to reduce the volume of striatal necrosis induced by middle cerebral artery occlusion. 16 Thus, the dopaminergic nigrostriatal pathway could be highly involved in the vulnerability of the striatum to ischemia, and glutamate-dopamine interactions may play a key role in striatal ischemic insult.…”