Endogenous adenosine A1 receptor activation underlies the transient post-ischemic rhythmic delta EEG activity

ObjectiveEmergence of slow EEG rhythms within the delta frequency band following an ischemic insult of the brain has long been considered a marker of irreversible anatomical damage. Here we investigated whether ischemic adenosine release and subsequent functional inhibition via the adenosine A1 receptor (A1R) contributes to post-ischemic delta activity.MethodsRats were subjected to episodes of non-injuring transient global cerebral ischemia (GCI) under chloral hydrate anesthesia.ResultsWe found that a GCI lasting only 10 s was enough to induce a brief discharge of rhythmic delta activity (RDA) with a peak frequency just below 1 Hz quantified as an increase by twofold of the 0.5–1.5 Hz spectral power. This post-ischemic RDA did not occur following administration of the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine. Nevertheless, a similar RDA could be induced in rats not subjected to GCI, by systemic administration of the A1R agonist N6-cyclopentyladenosine.ConclusionsOur data suggest that A1R activation at levels that occur following cerebral ischemia underlies the transient post-ischemic RDA.SignificanceIt is likely that the functional, thus potentially reversible, synaptic disconnection by A1R activation promotes slow oscillations in the cortical networks. This should be accounted for in the interpretation of early post-ischemic EEG delta activity.

► We introduced a new experimental model to investigate in vivo the transient post-ischemic electrocortical delta activity.
► We found that even brief, non-damaging, cerebral ischemic episodes release sufficient adenosine to promote delta activity via activation of A1 receptors.
► Interpretation of the acute post-ischemic delta activity should account for the functional, thus potentially reversible, connectivity impairment induced by adenosine.