White Matter Injury After Subarachnoid Hemorrhage

Stroke - Tập 46 Số 10 - Trang 2909-2915 - 2015
Yusuke Egashira1, Hao Zhao1, Ya Hua1, Richard F. Keep1, Guohua Xi1
1From the Department of Neurosurgery, University of Michigan, Ann Arbor.

Tóm tắt

Background and Purpose— We recently observed early white matter injury after experimental subarachnoid hemorrhage (SAH), but the underlying mechanisms are uncertain. This study investigated the potential role of matrix metalloproteinase (MMP)-9 in blood–brain barrier (BBB) disruption and consequent white matter injury. Methods— SAH was induced by endovascular perforation in adult male mice. The following 3 experiments were devised: (1) mice underwent magnetic resonance imaging at 24 h after SAH and were euthanized to determine BBB disruption and MMP-9 activation in white matter; (2) to investigate the role of MMP-9 in BBB disruption, lesion volumes on magnetic resonance imaging were compared between wild-type (WT) and MMP-9 knockout (MMP-9 −/− ) mice at 24 h after SAH; (3) WT and MMP-9 −/− mice underwent magnetic resonance imaging at 1 and 8 days after SAH to detect time-dependent changes in brain injury. Brains were used to investigate myelin integrity in white matter. Results— In WT mice with SAH, white matter showed BBB disruption (albumin leakage) and T2 hyperintensity on magnetic resonance imaging. MMP-9 activity was elevated at 24 h after SAH. MMP-9 −/− mice had less white matter T2 hyperintensity after SAH than WT mice. At 8 days after SAH, WT mice had decreased myelin integrity and MMP-9 −/− mice developed less white matter injury. Conclusions— SAH causes BBB disruption and consequent injury in white matter. MMP-9 plays an important role in those pathologies and could be a therapeutic target for SAH-induced white matter injury.

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Tài liệu tham khảo

10.1016/S1474-4422(09)70126-7

10.1007/s12975-013-0257-2

10.1161/01.str.0000015624.29071.1f

10.1186/1742-2094-11-2

10.1089/neu.1995.12.833

10.1212/01.wnl.0000216133.98416.b4

10.1159/000328248

10.1161/STROKEAHA.114.005307

10.1161/STROKEAHA.112.662312

10.1038/jcbfm.2010.137

10.1016/j.jneumeth.2007.08.004

10.1097/CCM.0b013e31829a8246

10.1016/j.brainres.2011.09.062

10.1186/1742-2094-10-105

10.1007/s12975-012-0232-3

10.1111/ejn.12179

10.1089/neu.2013.3080

10.1002/ana.24242

10.1016/j.neulet.2014.05.005

10.1002/glia.20169

10.1038/nm1735

10.3171/jns.2004.101.4.0633

10.1007/s10072-009-0192-x

10.1016/S1474-4422(05)70283-0

10.1159/000111560

10.1038/sj.jcbfm.9600354

10.1186/1742-2094-9-68

10.1097/01.WCB.0000053472.41007.F9

10.1038/nrn2495

10.1016/S0896-6273(00)80359-1

10.1002/(SICI)1097-4695(19981115)37:3<413::AID-NEU7>3.0.CO;2-8

10.1172/JCI65863

10.1074/jbc.M106089200

10.1158/0008-5472.CAN-09-1934

10.1038/nm1387

10.1002/glia.22320

10.1212/WNL.53.1.20

10.1161/01.STR.0000253500.32979.d1

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Stroke

Tập 46 Số 10

2909-2915

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