Specific ligand for a central type prostacyclin receptor attenuates neuronal damage in a rat model of focal cerebral ischemia

The neuroprotective effect of a central type prostacyclin receptor ligand was examined in a rat model of focal cerebral ischemia. Under halothane anesthesia, male Sprague-Dawley rats were subjected to left middle cerebral artery occlusion. A selective central type prostacyclin receptor ligand, 15-deoxy-(16-m-tolyl)-17,18,19,20-tetranorisocarbacyclin methylester, or a peripheral type prostacyclin receptor ligand, iloprost methylester, were administered intravenously immediately after ischemia. Twenty-four hours after ischemia, brain damage was evaluated. In separate experiments, concentrations of 15-deoxy-(16-in-tolyl)-17,18,19,20-tetranorisocarbacyclin in ischemic brain tissue were measured by injection of a tritium labeled compound. Treatment with 15-deoxy-(16-m-tolyl)-17,18,19,20-tetranorisocarbacyclin methylester (0.03 mg/kg) significantly (P<0.05) reduced the volume of brain damage by 35%. With this treatment, the concentration of this compound in the brain was more than 10 nM. Treatment with iloprost methylester did not show a neuroprotective effect. These results indicated that activation of a central type prostacyclin receptor attenuates ischemic brain damage. The present study demonstrated that the intravenous application of a central type prostacyclin receptor ligand could be a novel therapeutic agent for acute stroke. (C) 2002 Published by Elsevier Science B.V.