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-m-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.
AuthorsHiroyuki Takamatsu, Hideo Tsukada, Yumiko Watanabe, Yilong Cui, Yosky Kataoka, Takamitsu Hosoya, Masaaki Suzuki, Yasuyoshi Watanabe
JournalBrain research (Brain Res) Vol. 925 Issue 2 Pg. 176-82 (Jan 25 2002) ISSN: 0006-8993 [Print] Netherlands
PMID11792366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 15-deoxy-(16-m-tolyl)-17,18,19,20-tetranorisocarbacyclin methylester
  • 15-deoxy-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin
  • Ligands
  • Neuroprotective Agents
  • Receptors, Epoprostenol
  • Receptors, Prostaglandin
  • Epoprostenol
  • Animals
  • Brain (drug effects, metabolism, pathology)
  • Brain Chemistry
  • Brain Infarction (etiology, pathology, prevention & control)
  • Brain Ischemia (drug therapy, etiology, pathology)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Epoprostenol (administration & dosage, analogs & derivatives, analysis)
  • Infarction, Middle Cerebral Artery (complications, drug therapy, pathology)
  • Injections, Intravenous
  • Ligands
  • Male
  • Neurons (drug effects, pathology)
  • Neuroprotective Agents (administration & dosage)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Epoprostenol
  • Receptors, Prostaglandin (classification, metabolism)

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