Central Adenosine A2A Receptor Blockade Modulates Reperfusion Injury Following Bilateral Carotid Occlusion

Abstract

Prolonged oxygen and glucose deprivation to the brain of, if persistent, may eventually lead to neuronal death. In the present study, the effects of SCH 58261, a selective A2A antagonist that crosses the blood brain barrier (BBB) and 8-(4-sulfophenyl) theophylline (8-SPT), a non-selective A2A antagonist, that does not cross the BBB, were investigated on ischemia reperfusion injury (IR). Male Wistar rats (200 – 250 g) were divided into five groups: (i) sham-operated, (IR) (24h) pretreated with either (ii) vehicle; (iii) SCH 58261 (0.01 mg/kg); (iv), 8-SPT (2.5 mg/kg); or (v) their combination. Animals were anesthetized and submitted to occlusion of both common carotid arteries for 45 min. All treatments were administered i.p post carotid occlusion and exposed to 24 h reperfusion. Ischemic rats showed increased anxiety, locomotor activity and activity scores indicating habituation deficit. Both SCH 58261 and the combination treatments significantly reversed these effects as well as reducing LDH activity in the hipocampal homogenate, while 8-SPT elicited no change. IR increased (PGE2) accompanied by a decline in nitric oxide (NO) which were reversed by SCH 58261 and the combination, but not 8-SP. Moreover, histochemically, SCH58261 reversed hippocampal damage induced by IR. Hence, central blockade of adenosine A2A receptor ameliorates hippocampal damage following IR injury by halting inflammatory cascades.