title: Physiological studies of cortical spreading depression.
abstract: Cortical spreading depression (CSD) produces propagating waves of transient neuronal hyperexcitability followed by depression. CSD is initiated by K+ release following neuronal firing or electrical, mechanical or chemical stimuli. A triphasic (30-50 s) cortical potential transient accompanies localized transmembrane redistributions of K+, glutamate, Ca2+, Na+, Cl- and H+. Accumulated K+ in the restricted interstitial space can cause both further neuronal depolarisation and inward movement of K+ into astrocytes that buffers this increased extracellular K+ concentration ([K+])o. However, astrocyte interconnections may then propagate the CSD wave by K+ liberation through an opening of remote K+ channels by volume, Ca2+ or N-methyl-D-aspartate receptor activation. Changes in cerebral blood volume and in apparent water diffusion co-efficient (ADC) accompanying CSD were first studied using magnetic resonance imaging (MRI) in whole lissencephalic brains. Diffusion-weighted echoplanar imaging in gyrencephalic brains went on to demonstrate CSD features that paralleled classical migraine aura. The ADC activity persisted minutes/hours post KCl stimulus. Pixelwise analyses distinguished single primary events and multiple, spatially restricted, slower propagating, secondary events whose detailed features varied with the nature of the originating stimulus. These ADC changes varied reciprocally with T2*-weighted (i.e. referring to spin-spin relaxation times) waveforms reflecting local blood flow. There followed prolonged decreases in cerebral blood flow culminating in late cerebrovascular changes blocked by the antimigraine agent sumatriptan. CSD phenomena have possible translational significance for human migraine aura and other cerebral pathologies such as the peri-infarct depolarisation events that follow ischaemia and brain injury.
authors.affiliation: Cambridge Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Robinson Way, Cambridge CB1 5RH, UK.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Smith
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Bradley
authors.forename: Michael F
authors.initials: MF
authors.lastname: James
authors.forename: Christopher L-H
authors.initials: CL
authors.lastname: Huang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply* / Q000378:metabolism; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D006801:Humans; D011188:Potassium / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology
chemical_list: D011189:Potassium Chloride; D011188:Potassium