한빛사논문
- 조회3,789
Abstract
Ji Hae Seo1,2, Nobukazu Miyamoto1, Kazuhide Hayakawa1, Loc-Duyen D. Pham1, Takakuni Maki1, Cenk Ayata3, Kyu-Won Kim2,4,5, Eng H. Lo1,* and Ken Arai1,*
1Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
2NeuroVascular Coordination Research Center, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
3Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
4Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and
5Department of Internal Medicine, and Innovative Research Institute for Cell Therapy, Seoul National University, Seoul, Republic of Korea.
*Address correspondence to: Ken Arai or Eng H. Lo, Neuroprotection Research Laboratory, MGH East 149-2401, Charlestown, Massachusetts 02129, USA.
Oligodendrocyte precursor cells (OPCs) are thought to maintain homeostasis and contribute to long-term repair in adult white matter; however, their roles in the acute phase after brain injury remain unclear. Mice that were subjected to prolonged cerebral hypoperfusion stress developed white matter demyelination over time. Prior to demyelination, we detected increased MMP9 expression, blood-brain barrier (BBB) leakage, and neutrophil infiltration in damaged white matter. Notably, at this early stage, OPCs made up the majority of MMP9-expressing cells. The standard MMP inhibitor GM6001 reduced the early BBB leakage and neutrophil infiltration, indicating that OPC-derived MMP9 induced early BBB disruption after white matter injury. Cell-culture experiments confirmed that OPCs secreted MMP9 under pathological conditions, and conditioned medium prepared from the stressed OPCs weakened endothelial barrier tightness in vitro. Our study reveals that OPCs can rapidly respond to white matter injury and produce MMP9 that disrupts the BBB, indicating that OPCs may mediate injury in white matter under disease conditions.
논문정보
- Research article
- 2013년 01월 (BRIC 등록일 )
- 국내+국외 연구진
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