Effect of TTC-909 in a middle cerebral artery thrombosis model in stroke-prone spontaneously hypertensive rats.

Abstract

We investigated the effect of TTC-909, a preparation of the stable prostaglandin I(2) analogue clinprost (isocarbacyclin methylester; methyl 5-[(1S,5S,6R,7R)-7-hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl] bicyclo[3.3.0]oct-2-en-3-yl] pentanoate) incorporated into lipid microspheres, on infarct volume 24 h after photochemically induced thrombotic occlusion of the middle cerebral artery in stroke-prone spontaneously hypertensive rats (SHR). Under anesthesia, the photosensitizing dye rose bengal (20 mg/kg) was administered intravenously and photoirradiation with green light (wavelength 540 nm) on the middle cerebral artery above the rhinal fissure was achieved using a xenon lamp for 10 min. Infarct volume 24 h after the photochemically induced thrombotic occlusion of the middle cerebral artery was significantly larger in stroke-prone SHR than in Wistar rats. When TTC-909 in doses of 100, 300 and 900 ng/kg/h was intravenously infused for 3 h, starting immediately after the end of the 10-min photoirradiation, the infarct volume was dose-dependently reduced and was statistically significant at a dose of 900 ng/kg/h (p < 0.05). Ozagrel, a thromboxane A(2) synthetase inhibitor, significantly reduced the infarct volume. The model of photochemically induced thrombotic occlusion of the middle cerebral artery in stroke-prone SHR is very useful, because the cerebral infarction is large enough and reproducible. TTC-909 may be effective for the treatment of acute ischemic stroke.

• Authors: Yasuko Karasawa, Takehiko Hitomi, Hiroko Komiyama, Yoshihiko Isobe, Tsunefumi Kobayashi, Shigeru Yoshida, Shiro Nakaike, Hiroaki Araki
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 449 Issue 1-2 Pg. 127-133 (Aug 02 2002) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12163116 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Fibrinolytic Agents
• Methacrylates
• TTC 909
• Epoprostenol
• Thromboxane-A Synthase
• ozagrel

Topics

• Animals
• Brain (pathology)
• Enzyme Inhibitors (therapeutic use)
• Epoprostenol (analogs & derivatives, therapeutic use)
• Fibrinolytic Agents (therapeutic use)
• Infarction, Middle Cerebral Artery (drug therapy, pathology)
• Intracranial Thrombosis (drug therapy, pathology)
• Male
• Methacrylates (therapeutic use)
• Microspheres
• Rats
• Rats, Inbred SHR
• Rats, Wistar
• Thromboxane-A Synthase (antagonists & inhibitors)