Abstract W MP92: Role of Lipocalin 2 in Acute Ventricular Dilatation After Intraventricular Hemorrhage
Background: Acute hydrocephalus is a common complication following hemorrhagic stroke. Although recent studies demonstrated that intraventricular hemorrhage (IVH) causes hydrocephalus, the exact mechanism by which hydrocephalus develops after IVH are not well understood. Lipocalin 2 (LCN2), a siderophore-binding protein, is an acute phase protein in the brain. In the present study, we examined the role of LCN2 in ventricular dilatation in a mouse model of IVH.
Methods: First, female wild type C57BL/6 mice (WT, n=8) underwent a right intraventricular injection of hemoglobin (25mg/ml, 20 μl). Control mice (n=6) received saline injection. Ventricular volume was measured at 24 hours using magnetic resonance images. Second, female wild type and LCN2-deficient (LCN2-/-) mice had an intraventricular injection of hemoglobin (25mg/ml, n=5 for each; 50mg/ml, 20 μl, n=7 for WT and n=11 for LCN2-/-). They underwent magnetic resonance images at pre surgery and then 24 hours after surgery. All mice were euthanized at 24 hours after surgery. Brains were used for immunohistochemistry, immunofluorescence and Western blotting. Data are expressed as means±SD. P<0.05 was considered statistically significant.
Results: In wild type mice, injection of hemoglobin (25 mg/ml) rather than saline resulted in ventricular dilatation at 24 hours (12.5±2.4 vs. 8.6±1.5 mm3 in the control, p<0.01). Western blotting showed that LCN2 was significantly upregulated in the periventricular area after hemoglobin injection (26362±4165 vs. 2780±579 pixels in the control, p<0.01). LCN2 was expressed in astrocytes, whereas its receptor was detected in astrocytes and microglia/macrophages. Hemoglobin-induced ventricle enlargement was less in LCN2-/- mice (p<0.01) as was periventricular microglia activation (p<0.01). At a higher dose (50 mg/ml), hemoglobin resulted in high mortality in WT mice (86%), but much lower mortality in LCN2-/- mice (27%; p<0.05).
Conclusions: Our results indicate that LCN2 has a critical role in hemoglobin-induced ventricular dilatation.
Author Disclosures: H. Shishido: None. G. Xi: None. R.F. Keep: None. Y. Hua: None.
- © 2015 by American Heart Association, Inc.