Prostacyclin analogue TTC-909 reduces memory impairment in rats with cerebral embolism.
The effects of the stable prostacyclin analogue TTC-909 on memory impairment in the water maze task and on neuronal damage were studied in rats with cerebral embolism induced by injecting polyvinyl acetate (PVA) into the right internal carotid artery and the ensuing embolism extending out into the right middle cerebral artery. Areas supplied by the lenticulostriate artery were most markedly damaged. In the water maze test, the PVA-embolized rats took longer to reach the platform than did the nontreated control rats. To some extent, repeated administrations of TTC-909 (200 ng/kg, IV) overcame this impairment in water maze learning in the rats. We assume that the vasodilating effects of TTC-909 maintain this blood supply to the ischemic area and that TTC-909 prevents the development of thrombosis around the PVA particles in the arterial capillaries, as a result of antiplatelet aggregative effects. These two mechanisms are likely to be involved in memory improvement. TTC-909 may prove effective for treating subjects with stroke and other cerebrovascular disorders.
Department of Pharmacology, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Y
Y
Uchiyama-Tsuyuki
K
K
Kawashima
H
H
Araki
S
S
Otomo
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D001929:Brain Edema / Q000503:physiopathology / Q000523:psychology; D002536:Cerebral Arteries / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000503:physiopathology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism; D002542:Intracranial Embolism and Thrombosis / Q000139:chemically induced / Q000150:complications* / Q000523:psychology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D018696:Neuroprotective Agents; C068518:TTC 909; D011464:Epoprostenol; D005947:Glucose