Evidence that adenosine contributes to Leao's spreading depression in vivo

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 A₁ receptor (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.