title: Persisting depletion of brain glucose following cortical spreading depression, despite apparent hyperaemia: evidence for risk of an adverse effect of Leão's spreading depression.
abstract: Rapid sampling microdialysis (rsMD) directed towards the cerebral cortex has allowed identification of a combined time-series signature for glucose and lactate that characterizes peri-infarct depolarization in experimental focal ischaemia, but no comparable data exist for 'classical' cortical spreading depression (CSD) associated with hyperaemia in the normally perfused brain. Here, we examined the rsMD responses of dialysate glucose and lactate to five hyperaemic spreading depressions induced with intracortical microinjections, typically of 1 mol/L KCl, in open-skull preparations in five cats under chloralose anaesthesia. Depolarization was verified with microelectrodes, and laser speckle flowmetry was used to examine propagation of the events and perfusion responses near the MD probe. Ten minutes after depolarization, dialysate glucose fell and lactate rose by 28% and 58% respectively. There was no recovery of dialysate glucose 30 mins after depolarization. Mean baseline indicative cerebral blood flow was 25.5+/-4.1 mL/100 g/min and mean maximum hyperaemic increase was by 29.6+/-6 mL/100 g/min; hyperaemia remained present 30 mins after CSD. As CSD events are repetitive, frequent, and often clustered temporally in human acute brain injury, these results indicate a high risk of depletion of extracellular glucose in association with depolarization events of a pattern previously thought to be largely benign.
authors.affiliation: Department of Bioengineering, Imperial College, London, UK. phashemi@email.unc.edu
authors.forename: Parastoo
authors.initials: P
authors.lastname: Hashemi
authors.forename: Robin
authors.initials: R
authors.lastname: Bhatia
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Jens P
authors.initials: JP
authors.lastname: Dreier
authors.forename: Rudolf
authors.initials: R
authors.lastname: Graf
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Strong
authors.forename: Martyn G
authors.initials: MG
authors.lastname: Boutelle
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002415:Cats; D013181:Cortical Spreading Depression / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006940:Hyperemia / Q000378:metabolism* / Q000473:pathology*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D012307:Risk Factors
chemical_list: D019344:Lactic Acid; D005947:Glucose