2012年5月
Microglial cell activation is a source of metalloproteinase generation during hemorrhagic transformation
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
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- 巻
- 32
- 号
- 5
- 開始ページ
- 919
- 終了ページ
- 932
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/jcbfm.2012.11
- 出版者・発行元
- NATURE PUBLISHING GROUP
Hemorrhage and edema accompany evolving brain tissue injury after ischemic stroke. In patients, these events have been associated with metalloproteinase (MMP)-9 in plasma. Both the causes and cellular sources of MMP-9 generation in this setting have not been defined. MMP-2 and MMP-9 in nonhuman primate tissue in regions of plasma leakage, and primary murine microglia and astrocytes, were assayed by immunocytochemistry, zymography, and real-time RT-PCR. Ischemia-related hemorrhage was associated with microglial activation in vivo, and with the leakage of plasma fibronectin and vitronectin into the surrounding tissue. In strict serum-depleted primary cultures, by zymography, pro-MMP-9 was generated by primary murine microglia when exposed to vitronectin and fibronectin. Protease secretion was enhanced by experimental ischemia (oxygen-glucose deprivation, OGD). Primary astrocytes, on each matrix, generated only pro-MMP-2, which decreased during OGD. Microglia astrocyte contact enhanced pro-MMP-9 generation in a cell density-dependent manner under normoxia and OGD. Compatible with observations in a high quality model of focal cerebral ischemia, microglia, but not astrocytes, respond to vitronectin and fibronectin, found when plasma extravasates into the injured region. Astrocytes alone do not generate pro-MMP-9. These events explain the appearance of MMP-9 antigen in association with ischemia-induced cerebral hemorrhage and edema. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 919--932; doi:10.1038/jcbfm.2012.11; published online 22 February 2012
- リンク情報
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- DOI
- https://doi.org/10.1038/jcbfm.2012.11
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/22354151
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000303625900016&DestApp=WOS_CPL
- URL
- http://www.scopus.com/inward/record.url?eid=2-s2.0-84862777406&partnerID=MN8TOARS
- URL
- http://orcid.org/0000-0001-6337-8156
- ID情報
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- DOI : 10.1038/jcbfm.2012.11
- ISSN : 0271-678X
- ORCIDのPut Code : 28502370
- PubMed ID : 22354151
- SCOPUS ID : 84862777406
- Web of Science ID : WOS:000303625900016