title: White Matter Injury After Subarachnoid Hemorrhage: Role of Blood-Brain Barrier Disruption and Matrix Metalloproteinase-9.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Department of Neurosurgery, University of Michigan, Ann Arbor.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Egashira
authors.affiliation: From the Department of Neurosurgery, University of Michigan, Ann Arbor.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhao
authors.affiliation: From the Department of Neurosurgery, University of Michigan, Ann Arbor.
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
authors.affiliation: From the Department of Neurosurgery, University of Michigan, Ann Arbor.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.affiliation: From the Department of Neurosurgery, University of Michigan, Ann Arbor. guohuaxi@umich.edu.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D008279:Magnetic Resonance Imaging; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000473:pathology; D066127:White Matter / Q000378:metabolism* / Q000473:pathology
chemical_list: D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: blood–brain barrier; brain injuries; matrix metalloproteinase-9; subarachnoid hemorrhage; white matter