title: Acute white matter injury after experimental subarachnoid hemorrhage: potential role of lipocalin 2.
abstract: OBJECTIVE
  White matter injury occurs after subarachnoid hemorrhage (SAH) and has not been well studied. In this study, we investigated acute white matter injury in a mouse SAH model and the role of lipocalin 2 (LCN2) in that injury.
  
  
  METHODS
  SAH was induced by endovascular perforation in wild-type (WT) or LCN2 knockout (LCN2-/-) mice. Sham WT mice underwent the same procedure without perforation. MRI was performed 24 hours after SAH and the volumes of the T2-hyperintensity in white matter were measured. Immunohistochemistry was performed to determine white matter injury.
  
  
  RESULTS
  Mortality rates and SAH severity were not significantly different between WT and LCN2-/- animals. T2-hyperintensity in the white matter was observed in all WT animals at 24 hours after SAH (6.1±2.7 versus 0.06±0.07 mm3 in sham; P<0.001), and the volume of T2-hyperintensity tended to correlate with SAH severity (r=0.30; P=0.055). In WT animals with SAH, numerous LCN2-positive cells were observed in white matter. In contrast, LCN2-/- animals scarcely developed white matter T2-hyperintensity after SAH (0.5±0.5 mm3; P<0.001, versus WT). Markers of axonal damage and myelin degradation were increased in white matter after SAH in WT compared with those in LCN2-/- animals (P<0.05).
  
  
  CONCLUSIONS
  SAH results in an acute white matter injury at 24 hours in mice, and LCN2 plays an important role in 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: 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: D000209:Acute-Phase Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D056784:Leukoencephalopathies / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse
keywords: mice; subarachnoid hemorrhage