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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概要
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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.
著者
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ARAKI Hiroaki
Division of Pharmacy, Ehime University Hospital
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Araki H
Division Of Pharmacy Ehime University Hospital
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Araki Hiroaki
Department Of Clinical Pharmacology And Pharmacy Brain Science Ehime University Graduate School Of M
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Kobayashi Masayuki
Hematology Division National Cancer Center Hospital
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HINO Noriko
Department of Pharmacology, Research Center, Taisho Pharmaceutical Co. Ltd.
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KARASAWA Yasuko
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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KATSURA Yasuhiro
Pharmacological Research Department, Teijin Ltd.
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Hino Noriko
Pharmacology Laboratory Research Center Taisho Pharmaceutical Co. Ltd.
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Kurosaki Y
Department Of Clinical Pharmaceutical Science Graduate School Of Natural Science And Technology Okay
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Kurosaki Y
The Department Of Clinical Pharmaceutical Science Graduate School Of Natural Science And Technology
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Nakaike Shiro
Pharmacology Laboratory Research Center Taisho Pharmaceutical Co. Ltd.
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KATSUURA Yasuhiro
Pharmacological Research Department, Teijin Institute for Bio-Medical Research
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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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