Effect of TTC-909 on Cerebral Infarction Following Permanent Occlusion of the Middle Cerebral Artery in Stroke Prone Spontaneously Hypertensive Rats
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- Karasawa Yasuko
- Pharmacology Laboratory, Research Center, Taisho Pharmaceutical Co., Ltd.
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- Komiyama Hiroko
- Pharmacology Laboratory, Research Center, Taisho Pharmaceutical Co., Ltd.
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- Yoshida Shigeru
- Pharmacology Laboratory, Research Center, Taisho Pharmaceutical Co., Ltd.
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- Hino Noriko
- Pharmacology Laboratory, Research Center, Taisho Pharmaceutical Co., Ltd.
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- Katsuura Yasuhiro
- Pharmacological Research Department, Teijin Ltd.
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- Nakaike Shiro
- Pharmacology Laboratory, Research Center, Taisho Pharmaceutical Co., Ltd.
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- Araki Hiroaki
- Department of Hospital Pharmacy, Ehime University School of Medicine
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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.<br>
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 91 (4), 305-312, 2003
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001205177656576
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- NII論文ID
- 130000073689
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 6510789
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- PubMed
- 12719659
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- 本文言語コード
- en
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- データソース種別
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- NDL
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