Investigating paradoxical hysteresis effects in the mouse neocortical slice model

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dc.contributor.authorVoss, Logan J.
dc.contributor.authorBrock, Magdalena
dc.contributor.authorCarlsson, Cecilia
dc.contributor.authorSteyn-Ross, D. Alistair
dc.contributor.authorSteyn-Ross, Moira L.
dc.contributor.authorSleigh, James W.
dc.coverage.spatialNetherlandsen_NZ
dc.date.accessioned2012-05-23T03:06:51Z
dc.date.available2012-05-23T03:06:51Z
dc.date.copyright2012-01
dc.date.issued2012-01
dc.description.abstractClinically, anesthetic drugs show hysteresis in the plasma drug concentrations at induction versus emergence from anesthesia induced unconsciousness. This is assumed to be the result of pharmacokinetic lag between the plasma and brain effect-site and vice versa. However, recent mathematical and experimental studies demonstrate that anesthetic hysteresis might be due in part to lag in the brain physiology, independent of drug transport delay — so-called “neural inertia”. The aim of this study was to investigate neural inertia in the reduced neocortical mouse slice model. Seizure-like event (SLE) activity was generated by exposing cortical slices to no-magnesium artificial cerebrospinal fluid (aCSF). Concentration–effect loops were generated by manipulating SLE frequency, using the general anesthetic drug etomidate and by altering the aCSF magnesium concentration. The etomidate (24 μM) concentration–effect relationship showed a clear hysteresis, consistent with the slow diffusion of etomidate into slice tissue. Manipulation of tissue excitability, using either carbachol (50 μM) or elevated potassium (5 mM vs 2.5 mM) did not significantly alter the size of etomidate hysteresis loops. Hysteresis in the magnesium concentration–effect relationship was evident, but only when the starting condition was magnesium-containing “normal” aCSF. The in vitro cortical slice manifests pathway-dependent “neural inertia” and may be a valuable model for future investigations into the mechanisms of neural inertia in the cerebral cortex.en_NZ
dc.identifier.citationVoss, L.J., Block, M., Carlsson, C., Steyn-Ross, A., Steyn-Ross, M. & Sleigh, J.W. (2012). Investigating paradoxical hysteresis effects in the mouse neocortical slice model. European Journal of Pharmacology, 675(1-3), 26-31.en_NZ
dc.identifier.doi10.1016/j.ejphar.2011.11.045en_NZ
dc.identifier.urihttps://hdl.handle.net/10289/6356
dc.language.isoen
dc.publisherElsevieren_NZ
dc.relation.isPartOfEuropean Journal of Pharmacologyen_NZ
dc.relation.ispartofEuropean Journal of Pharmacology
dc.relation.urihttp://www.sciencedirect.com/science/article/pii/S0014299911015123en_NZ
dc.subjectanesthesiaen_NZ
dc.subjecthysteresisen_NZ
dc.subjectcortical sliceen_NZ
dc.subjectetomidateen_NZ
dc.titleInvestigating paradoxical hysteresis effects in the mouse neocortical slice modelen_NZ
dc.typeJournal Articleen_NZ
pubs.begin-page26en_NZ
pubs.elements-id37142
pubs.end-page31en_NZ
pubs.issue1-3en_NZ
pubs.volume675en_NZ
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