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

OBJECTIVE: Emergence 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 A(1) receptor (A(1)R) contributes to post-ischemic delta activity. METHODS: Rats were subjected to episodes of non-injuring transient global cerebral ischemia (GCI) under chloral hydrate anesthesia. RESULTS: We found that a GCI lasting only 10s 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 A(1)R antagonist 8-cyclopentyl-1,3-dipropylxanthine. Nevertheless, a similar RDA could be induced in rats not subjected to GCI, by systemic administration of the A(1)R agonist N(6)-cyclopentyladenosine. CONCLUSIONS: Our data suggest that A(1)R activation at levels that occur following cerebral ischemia underlies the transient post-ischemic RDA. SIGNIFICANCE: It is likely that the functional, thus potentially reversible, synaptic disconnection by A(1)R activation promotes slow oscillations in the cortical networks. This should be accounted for in the interpretation of early post-ischemic EEG delta activity.

Sleep deprivation attenuates experimental stroke severity in rats.

Indirect epidemiological and experimental evidence suggest that the severity of injury during stroke is influenced by prior sleep history. The aim of our study was to test the effect of acute sleep deprivation on early outcome following experimental stroke. Young male Sprague-Dawley rats (n=20) were subjected to focal cerebral ischemia by reversible right middle cerebral artery occlusion (MCAO) for 90 min. In 10 rats, MCAO was performed just after 6-h of total sleep deprivation (TSD) by "gentle handling", whereas the other rats served as controls. Neurological function during the first week after stroke was monitored using a battery of behavioral tests investigating the asymmetry of sensorimotor deficit (tape removal test and cylinder test), bilateral sensorimotor coordination (rotor-rod and Inclined plane) and memory (T-maze and radial maze). Following MCAO, control rats had impaired behavioral performance in all tests. The largest impairment was noted in the tape test where the tape removal time from the left forelimb (contralateral to MCAO) was increased by approximately 10 fold (p<0.01). In contrast, rats subjected to TSD had complete recovery of sensorimotor performance consistent with a 2.5 fold smaller infarct volume and reduced morphological signs of neuronal injury at day 7 after MCAO. Our data suggest that brief TSD induces a neuroprotective response that limits the severity of a subsequent stroke, similar to rapid ischemic preconditioning.