title: Lipocalin 2 and Blood-Brain Barrier Disruption in White Matter after Experimental Subarachnoid Hemorrhage.
abstract: We reported previously that subarachnoid hemorrhage (SAH) causes acute white matter injury in mice. In this study, we investigated lipocalin 2 (LCN2) mediated blood-brain barrier (BBB) disruption in white matter, which may lead to subsequent injury. SAH was induced by endovascular perforation in wild-type (WT) and LCN2-knockout (LCN2(-/-)) mice. Sham mice underwent the same procedure without perforation. Mice underwent magnetic resonance imaging (MRI) 24 h after SAH to confirm the development of T2-hyperintensity in white matter. Western blotting and immunohistochemistry were performed to elucidate the mechanisms of LCN2-mediated white matter injury and BBB disruption. It was confirmed that LCN2 expression was significantly increased in white matter of WT mice after SAH by Western blotting (versus sham; p < 0.05). Immunohistochemistry showed that LCN2 receptor 24p3R was expressed in oligodendrocytes, astrocytes, endothelial cells, and pericytes in the white matter. In WT mice with SAH, albumin leakage along the white matter was prominently observed and was consistent with T2-hyperintensity on MRI. As with our previous report, LCN2(-/-) mice scarcely developed T2-hyperintensity on MRI or albumin leakage in white matter. Our results suggest that BBB leakage occurs in white matter after SAH and that LCN2 contributes to SAH-induced BBB disruption.
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.|Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Egashira
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.affiliation: Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Iwama
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA. guohuaxi@umich.edu.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism*; D015153:Blotting, Western; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D007150:Immunohistochemistry; D000071068:Lipocalin-2 / Q000235:genetics* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009836:Oligodendroglia / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D000418:Albumins; D000071068:Lipocalin-2; C071332:Lcn2 protein, mouse
keywords: Blood-brain barrier; Lipocalin 2; Mice; Subarachnoid hemorrhage; White matter