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 I2 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 infarc...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2003-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319327136 |
| _version_ | 1818029950786076672 |
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| author | Yasuko Karasawa Hiroko Komiyama Shigeru Yoshida Noriko Hino Yasuhiro Katsuura Shiro Nakaike Hiroaki Araki |
| author_facet | Yasuko Karasawa Hiroko Komiyama Shigeru Yoshida Noriko Hino Yasuhiro Katsuura Shiro Nakaike Hiroaki Araki |
| author_sort | Yasuko Karasawa |
| collection | DOAJ |
| description | We investigated the effect of TTC-909, a drug preparation of the stable prostaglandin I2 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 A2 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. |
| first_indexed | 2024-12-10T05:27:50Z |
| format | Article |
| id | doaj.art-7cba233616044e5ca55108378a1f7fd2 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T05:27:50Z |
| publishDate | 2003-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-7cba233616044e5ca55108378a1f7fd22022-12-22T02:00:38ZengElsevierJournal of Pharmacological Sciences1347-86132003-01-01914305312Effect of TTC-909 on Cerebral Infarction Following Permanent Occlusion of the Middle Cerebral Artery in Stroke Prone Spontaneously Hypertensive RatsYasuko Karasawa0Hiroko Komiyama1Shigeru Yoshida2Noriko Hino3Yasuhiro Katsuura4Shiro Nakaike5Hiroaki Araki6Pharmacology Laboratory, Research Center, Taisho Pharmaceutical Co., Ltd., Yoshino-cho 1-403, Saitama 330-8530, JapanPharmacology Laboratory, Research Center, Taisho Pharmaceutical Co., Ltd., Yoshino-cho 1-403, Saitama 330-8530, JapanPharmacology Laboratory, Research Center, Taisho Pharmaceutical Co., Ltd., Yoshino-cho 1-403, Saitama 330-8530, JapanPharmacology Laboratory, Research Center, Taisho Pharmaceutical Co., Ltd., Yoshino-cho 1-403, Saitama 330-8530, JapanPharmacological Research Department, Teijin Ltd., 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, JapanPharmacology Laboratory, Research Center, Taisho Pharmaceutical Co., Ltd., Yoshino-cho 1-403, Saitama 330-8530, JapanDepartment of Hospital Pharmacy, Ehime University School of Medicine, Shiktsukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, JapanWe investigated the effect of TTC-909, a drug preparation of the stable prostaglandin I2 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 A2 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.http://www.sciencedirect.com/science/article/pii/S1347861319327136 |
| spellingShingle | Yasuko Karasawa Hiroko Komiyama Shigeru Yoshida Noriko Hino Yasuhiro Katsuura Shiro Nakaike Hiroaki Araki Effect of TTC-909 on Cerebral Infarction Following Permanent Occlusion of the Middle Cerebral Artery in Stroke Prone Spontaneously Hypertensive Rats Journal of Pharmacological Sciences |
| title | Effect of TTC-909 on Cerebral Infarction Following Permanent Occlusion of the Middle Cerebral Artery in Stroke Prone Spontaneously Hypertensive Rats |
| title_full | Effect of TTC-909 on Cerebral Infarction Following Permanent Occlusion of the Middle Cerebral Artery in Stroke Prone Spontaneously Hypertensive Rats |
| title_fullStr | Effect of TTC-909 on Cerebral Infarction Following Permanent Occlusion of the Middle Cerebral Artery in Stroke Prone Spontaneously Hypertensive Rats |
| title_full_unstemmed | Effect of TTC-909 on Cerebral Infarction Following Permanent Occlusion of the Middle Cerebral Artery in Stroke Prone Spontaneously Hypertensive Rats |
| title_short | Effect of TTC-909 on Cerebral Infarction Following Permanent Occlusion of the Middle Cerebral Artery in Stroke Prone Spontaneously Hypertensive Rats |
| title_sort | effect of ttc 909 on cerebral infarction following permanent occlusion of the middle cerebral artery in stroke prone spontaneously hypertensive rats |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319327136 |
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