DSpace About DSpace Software 日本語

01 奈良県立医科大学 >
012 大学院 >
0122 学位請求論文 >
01221 博士論文(医学) >
2012年度 >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/2790

Title: ADAMTS13 gene deletion enhances plasma high-mobility group box1 elevation and neuroinflammation in brain ischemia-reperfusion injury.
Other Titles: ADAMTS13 遺伝子欠損は脳虚血再灌流傷害における血漿high mobility group box1 の上昇を促進し神経炎症を悪化させる。
Authors: Fujioka, Masayuki
Nakano, Takafumi
Hayakawa, Kazuhide
Irie, Keiichi
Akitake, Yoshiharu
Sakamoto, Yuya
Mishima, Kenichi
Muroi, Carl
Yonekawa, Yasuhiro
Banno, Fumiaki
Kokame, Koichi
Miyata, Toshiyuki
Nishio, Kenji
Okuchi, Kazuo
Iwasaki, Katsunori
Fujiwara, Michihiro
Siesjö, Bo K.
Keywords: Brain ischemia–reperfusion
High-mobility group box1
Von Willebrand factor
Thrombotic thrombocytopenic purpura
Issue Date: Oct-2012
Publisher: Springer / Società italiana di neurologia
Citation: Neurological sciences Vol.33 No.5 p.1107-1115
Abstract: Highly adhesive glycoprotein von Willebrand factor (VWF) multimer induces platelet aggregation and leukocyte tethering or extravasation on the injured vascular wall, contributing to microvascular plugging and inflammation in brain ischemia–reperfusion. A disintegrin and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) cleaves the VWF multimer strand and reduces its prothrombotic and proinflammatory functions. Although ADAMTS13 deficiency is known to amplify post-ischemic cerebral hypoperfusion, there is no report available on the effect of ADAMTS13 on inflammation after brain ischemia. We investigated if ADAMTS13 deficiency intensifies the increase of extracellular HMGB1, a hallmark of post-stroke inflammation, and exacerbates brain injury after ischemia–reperfusion. ADAMTS13 gene knockout (KO) and wild-type (WT) mice were subjected to 30-min middle cerebral artery occlusion (MCAO) and 23.5-h reperfusion under continuous monitoring of regional cerebral blood flow (rCBF). The infarct volume, plasma high-mobility group box1 (HMGB1) level, and immunoreactivity of the ischemic cerebral cortical tissue (double immunofluorescent labeling) against HMGB1/NeuN (neuron-specific nuclear protein) or HMGB1/MPO (myeloperoxidase) were estimated 24 h after MCAO. ADAMTS13KO mice had larger brain infarcts compared with WT 24 h after MCAO (p < 0.05). The rCBF during reperfusion decreased more in ADAMTS13KO mice. The plasma HMGB1 increased more in ADAMTS13KO mice than in WT after ischemia–reperfusion (p < 0.05). Brain ischemia induced more prominent activation of inflammatory cells co-expressing HMGB1 and MPO and more marked neuronal death in the cortical ischemic penumbra of ADAMTS13KO mice. ADAMTS13 deficiency may enhance systemic and brain inflammation associated with HMGB1 neurotoxicity, and aggravate brain damage in mice after brief focal ischemia. We hypothesize that ADAMTS13 protects brain from ischemia–reperfusion injury by regulating VWF-dependent inflammation as well as microvascular plugging.
Description: 博士(医学)・乙第1310号・平成25年3月15日
© Springer International Publishing AG,2012
URI: http://hdl.handle.net/10564/2790
ISSN: 15901874
Appears in Collections:2012年度

Files in This Item:

File Description SizeFormat
01本文の要旨.pdf本文の要旨237.29 kBAdobe PDFView/Open
02審査要旨.pdf審査要旨731.54 kBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.


Valid XHTML 1.0! DSpace Software Copyright © 2002-2010  Duraspace - Feedback