title: Evidence that adenosine contributes to Leao's spreading depression in vivo.
abstract: Leao's spreading depression of cortical activity is a propagating silencing of neuronal activity resulting from spreading depolarization (SD). We evaluated the contributions of action potential (AP) failure and adenosine A1receptor (A1R) activation to the depression of evoked and spontaneous electrocorticographic (ECoG) activity after SD in vivo, in anesthetized mice. We compared depression with SD-induced effects on AP-dependent transmission, and synaptic potentials in the transcallosal and thalamocortical pathways. After SD, APs recovered rapidly, within 1-2 min, as demonstrated by evoked activity in distant projection targets. Evoked corticocortical postsynaptic potentials recovered next, within ∼5 min. Spontaneous ECoG and evoked thalamocortical postsynaptic potentials recovered together, after ∼10-15 min. The duration of ECoG depression was shortened 20% by systemic (10 mg/kg) or focal (30 µM) administration of A1R competitive antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). ECoG depression was also shortened by focal application of exogenous adenosine deaminase (ADA; 100 U/mL), and conversely, was prolonged 50% by the non-competitive ADA inhibitor deoxycoformycin (DCF; 100 µM). We concluded that while initial depolarization block is brief, adenosine A1R activation, in part, contributes to the persistent secondary phase of Leao's cortical spreading depression.
authors.affiliation: Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
authors.forename: Britta E
authors.initials: BE
authors.lastname: Lindquist
authors.affiliation: Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
authors.forename: C William
authors.initials: CW
authors.lastname: Shuttleworth
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000378:metabolism*; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D000069280:Electrocorticography; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D055366:Synaptic Potentials / Q000187:drug effects
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D000241:Adenosine
keywords: Spreading depression; adenosine; energy metabolism; evoked potentials; synapses/dendrites