Effect of TTC-909 on cerebral infarction following permanent occlusion of the middle cerebral artery in stroke prone spontaneously hypertensive rats.
We investigated the effect of TTC-909, a drug 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 cerebral infarction 7 days after permanent occlusion of the middle cerebral artery (MCA) in stroke prone spontaneously hypertensive rats (SHRSP). Under the anesthesia, the MCA was permanently occluded above the rhinal fissure. In schedule 1, vehicle or TTC-909 was injected i.v. once daily over 7 days starting immediately after MCA occlusion. In schedule 2, vehicle or TTC-909 was infused for 3 h starting immediately after MCA occlusion. In schedule 3, vehicle or TTC-909 was infused for 3 h starting immediately after MCA occlusion followed by bolus injection once daily over 6 days. Seven days later, the infarct volume was estimated following hematoxylin and eosin staining. Cerebral infarction produced by permanent occlusion of MCA was limited to the cerebral cortex. While this volume was reduced significantly in case of schedule 3, the infarct volume was not reduced significantly in schedules 1 and 2. Ozagrel, a thromboxane A(2) synthetase inhibitor, had no effect on the infarct volume in schedule 3. These results suggest that cerebral infarction can be developed progressively not only during the first few hours but also after a permanent occlusion of MCA in SHRSP. TTC-909 inhibited cerebral infarction, maybe by improving cerebral blood flow and by protecting against neuronal damage.
Pharmacology Laboratory, Research Center, Taisho Pharmaceutical Co. Ltd., Yoshino-cho 1-403, Saitama 330-8530, Japan.
Yasuko
Y
Karasawa
Hiroko
H
Komiyama
Shigeru
S
Yoshida
Noriko
N
Hino
Yasuhiro
Y
Katsuura
Shiro
S
Nakaike
Hiroaki
H
Araki
D000818:Animals; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000188:drug therapy / Q000473:pathology
C068518:TTC 909; D011464:Epoprostenol