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ID 49926
フルテキストURL
著者
Takamiya, M. Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Miyamoto, Y. Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci
Yamashita, T. Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol ORCID Kaken ID
Ohta, Y.
抄録
Reactive oxygen species (ROS) are major exacerbation factor in acute ischemic stroke, and thrombolytic agent tissue plasminogen activator (tPA) may worsen motor function and cerebral infarcts. The platinum nanoparticle (nPt) is a novel ROS scavenger, and thus we examined the clinical and neuroprotective effects of nPt in ischemic mouse brains. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min and divided into the following four groups by intravenous administration upon reperfusion, vehicle, tPA, tPA + nPt, and nPt. At 48 h after tMCAO, motor function, infarct volume, immunohistochemical analyses of neurovascular unit (NVU), in vivo imaging of matrix metalloproteinase (MMP), and zymography for MMP-9 activity were examined. Superoxide anion generation at 2 h after tMCAO was also examined with hydroethidine (HEt). As a result, administration of tPA deteriorated the motor function and infarct volume as compared to vehicle. In vivo optical imaging of MMP showed strong fluorescent signals in affected regions of tMCAO groups. Immunohistochemical analyses revealed that tMCAO resulted in a minimal decrease of NAGO and occludin, but a great decrease of collagen IV and a remarkable increase of MMP-9. HEt stain showed increased ROS generation by tMCAO. All these results became pronounced with tPA administration, and were greatly reduced by nPt. The present study demonstrates that nPt treatment ameliorates neurological function and brain damage in acute cerebral infarction with neuroprotective effect on NVU and inactivation of MMP-9. The strong reduction of ROS production by nPt could account for these remarkable neurological and neuroprotective effects against ischemic stroke.
キーワード
platinum nanoparticle
cerebral ischemia
free radical scavenger
neuroprotection
matrix metalloproteinase-9
tissue plasminogen activator
発行日
2012-09-27
出版物タイトル
Neuroscience
221巻
開始ページ
47
終了ページ
55
ISSN
0306-4522
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1016/j.neuroscience.2012.06.060
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/49728
言語
English
著作権者
(c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
論文のバージョン
author
査読
有り
DOI
Web of Science KeyUT