Cerebral ischemia induces a rapid suppression of spontaneous brain rhythms prior to major alterations in ionic homeostasis. It was found in vitro during ischemia that the rapidly formed adenosine, resulting from the intracellular breakdown of ATP, may inhibit synaptic transmission via the A1 receptor subtype. The link between endogenous A1 receptor activation during ischemia and the suppression of spontaneous electrocortical activity has not yet been established in the intact brain. The aim of this study was to investigate in vivo the effects of A1 receptor antagonism by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) on the time to electrocortical suppression during global cerebral ischemia. Adult male Wistar rats under chloral hydrate anesthesia were subjected to 1-min transient “four-vessel occlusion” ischemic episodes, separated by 20-min reperfusion. The rats were injected intraperitoneally with either 1.25 mg/kg DPCPX dissolved in 2 ml/kg dimethyl sulfoxide (DMSO) or the same volume of DMSO alone, 15 min before the third ischemic episode. Time to electrocortical suppression was estimated based on the decay of the root mean square of two-channel electrocorticographic recordings. During the first two ischemic episodes, electrocortical suppression appeared after ∼12 s in both groups. After DMSO administration, ischemic suppression remained unchanged. After DPCPX administration, the time to electrocortical suppression was increased by ∼10 s, and bursts of activity were recorded during the entire ischemia. These effects disappeared within 15 h after DPCPX administration. Our data provide evidence that during cerebral ischemia endogenous activation of A1 receptors accelerates the electrical “shut-down” of the whole brain.
EEG Suppression and Anoxic Depolarization: Influences on Cerebral Oxygenation during Ischemia
