Inhibition of Neutrophil Migration by a Protein Kinase Inhibitor for the Treatment of Ischemic Brain Infarction
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概要
- 論文の詳細を見る
This study investigated the therapeutic potential of agents that inhibited neutrophil infiltration in cerebral ischemic infarction. The migration of neutrophils elicited by N-formyl-methionyl-leucyl-phenylalanine, tumor necrosis factor, C5a or platelet-activating factor was potently inhibited by fasudil, an inhibitor of protein kinases including rho kinase, protein kinase C and myosin light chain kinase, and hydroxy fasudil, a metabolite of fasudil, in vitro. In a microembolism model in rats, myeloperoxidase-quantified neutrophil accumulation in the ischemic brain was observed 24 hr after embolization. Intravenous administration of fasudil prevented the accumulation of neutrophils. In rats given fasudil, myeloperoxidase activity in the ipsilateral hemisphere (0.04±0.01 unit/g wet tissue) was significantly lower than that in ischemic rats (0.11±0.02 unit/g wet tissue). Fasudil also significantly reduced the size of the infarct area and improved neurological functions. These results suggest that neutrophil infiltration into the ischemic brain is involved in the pathogenesis of ischemic injury and that inhibiting neutrophil infiltration may provide an effective therapeutic intervention to reduce ischemic injury.
- 社団法人 日本薬理学会の論文
- 1999-05-01
著者
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Yoshida Jun
Department Of Neurosurgery Nagoya University Graduate School Of Medicine
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SUZUKI Yoshio
Department of Pharmacology, Faculty of Pharmacy, Meijo University
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Shibuya Masato
Department Of Neurosurgery Chukyo Hospital
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Shibuya Masato
Department Of Media And Image Technology Faculty Of Engineering Tokyo Polytechnic University
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Satoh S
Scientific Affairs & Sales Promotion Department Asahi Kasei Pharma Corporation
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Asano T
Institute Of Life Science Research Asahi Kasei Corporation
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Asano Toshio
Laboratory For Pharmacology Asahi Chemical Industry
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Ikegaki Ichiro
Laboratory For Pharmacology Asahi Chemical Industry
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SATOH Shin-ichi
Laboratory for Pharmacology, Asahi Chemical Industry
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KOBAYASHI Teruki
Laboratory for Pharmacology, Asahi Chemical Industry
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HITOMI Asako
Laboratory for Pharmacology, Asahi Chemical Industry
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Hitomi Asako
Laboratory For Pharmacology Asahi Chemical Industry
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Kobayashi Teruki
Laboratory For Pharmacology Asahi Chemical Industry
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Yoshida Jun
Department Of Basic Science Graduate School Of Arts And Sciences The University Of Tokyo
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Shibuya Masato
Department Of Forest Science Faculty Of Agriculture Hokkaido University
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Suzuki Yoshio
Department Of Electronics Fukuoka Institute Of Technology
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Suzuki Yoshio
Department Of Neurosurgery Nagoya Daini Red Cross Hospital
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Suzuki Yoshio
Department Of Chemical Science & Technology Faculty Of Engineering Kyushu University
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