title: Persistent increase in oxygen consumption and impaired neurovascular coupling after spreading depression in rat neocortex.
abstract: Cortical spreading depression (CSD) is associated with a dramatic failure of brain ion homeostasis and increased energy metabolism. There is strong clinical and experimental evidence to suggest that CSD is the mechanism of migraine, and involved in progressive neuronal injury in stroke and head trauma. Here we tested the hypothesis that single episodes of CSD induced acute hypoxia, and prolonged impairment of neurovascular and neurometabolic coupling. Cortical spreading depression was induced in rat frontal cortex, whereas cortical electrical activity and local field potentials (LFPs) were recorded by glass microelectrodes, cerebral blood flow (CBF) by laser-Doppler flowmetry, and tissue oxygen tension (tpO(2)) with polarographic microelectrodes. Cortical spreading depression increased cerebral metabolic rate of oxygen (CMRO(2)) by 71%+/-6.7% and CBF by 238%+/-48.1% for 1 to 2 mins. For the following 2 h, basal tpO(2) and CBF were reduced whereas basal CMRO(2) was persistently elevated by 8.1%+/-2.9%. In addition, within first hour after CSD we found impaired neurovascular coupling (LFP versus CBF), whereas neurometabolic coupling (LFP versus CMRO(2)) remained unaffected. Impaired neurovascular coupling was explained by both reduced vascular reactivity and suppressed function of cortical inhibitory interneurons. The protracted effects of CSD on basal CMRO(2) and neurovascular coupling may contribute to cellular dysfunction in patients with migraine and acutely injured cerebral cortex.
authors.affiliation: Department of Neuroscience and Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Piilgaard
authors.forename: Martin
authors.initials: M
authors.lastname: Lauritzen
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D004594:Electrophysiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D009435:Synaptic Transmission / Q000502:physiology