Acute White Matter Injury After Experimental Subarachnoid Hemorrhage Potential Role of Lipocalin 2

Background and Purpose-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 mm(3) 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 mm(3); 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.