White Matter Injury After Subarachnoid Hemorrhage

<jats:sec> <jats:title>Background and Purpose—</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods—</jats:title> <jats:p> 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 <jats:sup>−/−</jats:sup> ) mice at 24 h after SAH; (3) WT and MMP-9 <jats:sup>−/−</jats:sup> 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. </jats:p> </jats:sec> <jats:sec> <jats:title>Results—</jats:title> <jats:p> 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 <jats:sup>−/−</jats:sup> 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 <jats:sup>−/−</jats:sup> mice developed less white matter injury. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>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.</jats:p> </jats:sec>