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

Academic Department of Anaesthesia and Intensive Care, The Royal London and St Bartholomew's School of Medicine and Dentistry, Royal London Hospital, Whitechapel, UK.
BJA British Journal of Anaesthesia (Impact Factor: 4.35). 04/2001; 86(4):550-4.
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Mechanism of sevoflurane preconditioning-induced cerebral ischemic tolerance is unclear. This study investigates the role of N-myc downstream-regulated gene-2 (NDRG2) in the neuroprotection of sevoflurane preconditioning in ischemic model both in vivo and in vitro.
    Anesthesiology 05/2014; DOI:10.1097/ALN.0000000000000314 · 6.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Isoflurane, desflurane and sevoflurane all preserve cerebrovascular carbone dioxide (CO2) reactivity. They are all concentration-dependant cerebral vasodilatators and decrease cerebral metabolism. Sevoflurane induces the smallest cerebral vasodilatation and preserve cerebral autoregulation up to 1.5 CAM, compared to isoflurane and desflurane which impair it upon 1 CAM. Propofol has been compared to inhaled agents. Propofol preserve cerebrovascular CO2 reactivity, blood flow-metabolism coupling, cerebral autoregulation and has no vasodilatation effect. None of the three inhaled agents induce any clinical relevant increase of intracranial pressure (ICP), but studies were conducted in patients without any intracranial hypertension (ICHT). However, compared to propofol, ICP and brain swelling were higher with inhaled agents, more with isoflurane compared to sevoflurane. Finally, neuroprotective properties have been described in experimental model for all the inhaled agents but clinical proofs are still lacking. In conclusion, for intracranial surgery without any ICHT inhaled agents can be used as a maintenance anesthetic with a preference for sevoflurane. In case of ICHT or a risk of ICHT during the surgery, propofol is preferred for it slightest effect on ICP and cerebral hemodynamic.
    Annales francaises d'anesthesie et de reanimation 10/2012; 31(10):e229–e234. DOI:10.1016/j.annfar.2012.08.003 · 0.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The neuroprotective properties for certain medical gases have been observed for decades, leading to extensive research that has been widely reported and continues to garner interest. Common, gases including oxygen, hydrogen, carbon dioxide and nitric oxide, volatile anesthetics such as, isoflurane, sevoflurane, halothane, enflurane and desflurane, non-volatile anesthetics xenon and, nitrous oxide, inert gases such as helium, argon and even gases classically considered to be toxic (e.g., hydrogen sulfide and carbon monoxide) have all been supported by evidence alluding to their use as, potential neuroprotective agents. A wide range of neural injury types such as ischemic/hemorrhagic, stroke, subarachnoid hemorrhage, traumatic brain injury, perinatal hypoxic-ischemic brain injuries, neurodegenerative disease as well as spinal cord ischemia, have been used as platforms for studying, the neuroprotective effects of these gases, yet until now, none of the gases has been widely introduced, into clinical use specifically for protection against neural injury. Insufficient clinical data together with, contradictory paradigms and results further hinders the clinical. However, pre-clinical models suggest, that, despite the various classes of gases and the broad range of injuries to which medical gases confer, protection, several underlying mechanisms for their neuroprotective properties are similar. In this, review, we summarize the literature concerning the neuroprotective effect of each gas and its, underlying mechanisms, extract common targets reported for the neuroprotective effects of different, gases, highlight the conflicting observations from clinical trials and further discuss the possible, hindrances impeding clinical applications in order to propose future research perspectives and, therapeutic exploitations.
    Progress in Neurobiology 01/2014; DOI:10.1016/j.pneurobio.2014.01.001 · 10.30 Impact Factor

Full-text (2 Sources)

Available from
Oct 30, 2014