White Matter Injury After Subarachnoid Hemorrhage: Role of Blood–Brain Barrier Disruption and Matrix Metalloproteinase-9. Issue 10 (October 2015)

• Record Type: Journal Article
• Authors: Egashira, Yusuke; Zhao, Hao; Hua, Ya; Keep, Richard F.; Xi, Guohua
• Is Part Of: Stroke. Volume 46:Issue 10(2015)
• Publication Date: 2015-10
• Subjects: blood–brain barrier -- brain injuries -- matrix metalloproteinase-9 -- subarachnoid hemorrhage -- white matter; Cerebrovascular disease -- Periodicals; Cerebral circulation -- Periodicals; 616.81
• DOI: 10.1161/STROKEAHA.115.010351
• Languages: English
• ISSNs: 0039-2499

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text.