Cerebral ischemia in gerbils: postischemic administration of cyclohexyl adenosine and 8-sulfophenyl-theophylline

Adenosine agonists have now been shown by several laboratories to have profound neuroprotective effects when administered either pre- or postischemia. In an effort to determine whether these effects are centrally mediated, the effects of the non-brain-permeable adenosine receptor antagonist 8-sulfophenyl-theophylline (8-SPTH) on cyclohexyladenosine (CHA) -mediated protection was determined. Both survival and neurologic outcome were assessed in gerbils following 30 minutes of bilateral carotid occlusion. A dose of 2 mg/kg of CHA 5 minutes postreperfusion resulted in highly significant increases in survival relative to saline injected controls. Administration of doses of 8-SPTH sufficient to normalize the hypotension observed with CHA resulted in the same degree of postischemic protection. Similar results were obtained when neurologic status was evaluated. The results indicate that the neuroprotective effects of CHA are apparently centrally mediated.