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- 上田 雅之
- 日本医科大学大学院医学研究科神経内科学
書誌事項
- タイトル別名
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- Brain Protection Therapy for Ischemic Brain Injury
- キョケツセイ ノウ ソンショウ ニ タイスル ノウ ホゴ リョウホウ
この論文をさがす
説明
Therapeutic strategies for protecting the brain against ischemic injury aim to salvage the ischemic penumbra or to expand the therapeutic time window, or both. We have investigated the protective effects of several agents using a rat model of transient focal cerebral ischemia. Our experimental studies have identified the following agents with attractive protective mechanisms against brain ischemia: the free-radical scavenger edaravone (MCI-186), the immunosuppressant tacrolimus (FK506), bone marrow stromal cells (BMSCs) /bone marrow mononuclear cells (BMMCs), the ω3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), and the hydroxymethyl glutaryl coenzyme A reductase inhibitor atorvastatin. The free-radical scavenger MCI-186 has a Bax/Bcl-2-dependent antiapoptotic mechanism in a rat model of transient focal cerebral ischemia. The therapeutic time window for FK506 in rat transient focal ischemia is from 60 to 120 minutes after ischemia induction, and mild hypothermia (35°C) expands the therapeutic time window up to 120 minutes after ischemia induction. Intravenous transplantation of BMSCs 120 minutes after ischemia induction, which is out of the therapeutic time window for FK506 alone, is neuroprotective when performed in conjunction with FK506 injection. Intra-arterial transplantation of BMMCs is more protective against transient focal cerebral ischemia than is intravenous transplantation of BMMCs. Repeated intravenous transplantation of BMMCs achieves further neuroprotection against ischemic brain injury. Pretreatment with ethyl-EPA inhibits endothelial Rho-kinase activation and reduces tissue oxidative stress following transient ischemia, resulting in strong neuroprotection. The long-term protective effects of atorvastatin against brain ischemia require continuous oral administration after ischemia/reperfusion. All of the agents used in our experimental studies are established therapies for ischemic stroke or other disorders. Further investigations are needed before such experimental brain protection strategies can be applied clinically.
収録刊行物
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- 日本医科大学医学会雑誌
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日本医科大学医学会雑誌 10 (4), 164-171, 2014
日本医科大学医学会
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詳細情報 詳細情報について
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- CRID
- 1390282680207921920
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- NII論文ID
- 130004705181
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- NII書誌ID
- AA1200910X
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- ISSN
- 18802877
- 13498975
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- NDL書誌ID
- 025866837
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- NDL
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- CiNii Articles
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- 使用不可