スダ サトシ   SUDA Satoshi
  須田 智
   所属   埼玉医科大学  医学部 国際医療センター 神経内科・脳卒中内科
   職種   教授
論文種別 学術雑誌(原著)
言語種別 英語
査読の有無 査読あり
表題 Effect of repeated allogeneic bone marrow mononuclear cell transplantation on brain injury following transient focal cerebral ischemia in rats
掲載誌名 正式名:LIFE SCIENCES
ISSNコード:0024-3205/1879-0631
出版社 PERGAMON-ELSEVIER SCIENCE LTD
巻・号・頁 95(1),22-28頁
著者・共著者 Fumio Kamiya,Masayuki Ueda,Chikako Nito,Nobuo Kamiya,Toshiki Inaba,Satoshi Suda,Tomonari Saito,Kanako Muraga,Yasuo Katayama
発行年月 2014/01
概要 Aims: Transplantation of bone marrow mononuclear cells (BMMCs) exerts neuroprotection against cerebral ischemia. We examined the therapeutic timepoint of allogeneic BMMC transplantation in a rat model of focal cerebral ischemia, and determined the effects of repeated transplantation outside the therapeutic window.
Main methods: Male Sprague-Dawley rats were subjected to 90 minute focal cerebral ischemia, followed by intravenous administration of 1 x 10(7) allogeneic BMMCs or vehicle at 0,3 or 6 h after reperfusion or 2 x 10(7) BMMCs 6 h after reperfusion. Other rats administered 1 x 10(7) BMMCs at 6 h after reperfusion received additional BMMC transplantation or vehicle 9 h after reperfusion. Infarct volumes, neurological deficit scores and immunohistochemistry were evaluated 24 or 72 h after reperfusion.
Key findings: Infarct volumes at 24 h were significantly decreased in transplantation rats at 0 and 3 h, but not at 6 h, after reperfusion, compared to vehicle-treatment. Even high dose BMMC transplantation at 6 h after reperfusion was ineffective. Repeated BMMC transplantation at 6 and 9 h after reperfusion reduced infarct volumes and significantly improved neurological deficit scores at 24 and 72 h. Immunohistochemistry showed repeated BMMC transplantation reduced ionized calcium-binding adapter molecule 1, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine expression at 24 and 72 h after reperfusion.
Significance: Intravenous allogeneic BMMCs were neuroprotective following transient focal cerebral ischemia, and the therapeutic time window of BMMC transplantation was >3 h and <6 h after reperfusion in this model. Repeated transplantation at 6 and 9 h after reperfusion suppressed inflammation and oxidative stress in ischemic brains, resulting in improved neuroprotection. (C) 2013 Elsevier Inc. All rights reserved.
DOI 10.1016/j.lfs.2013.12.016
PMID 24368140