Role of lipocalin-2 in brain injury after intracerebral hemorrhage

Lipocalin-2 (LCN2) is a siderophore-binding protein involved in cellular iron transport and neuroinflammation. Both iron and inflammation are involved in brain injury after intracerebral hemorrhage (ICH) and this study examined the role of LCN2 in such injury. Male adult C57BL/6 wild-type (WT) or LCN2-deficient (LCN2(-/-)) mice had an intracerebral injection of autologous blood or FeCl2. Control animals had a sham operation or saline injection. T2-weighted magnetic resonance imaging and behavioral tests were performed at days 1, 3, 7, 14, and 28 after injection. In WT mice, brain LCN2 levels were increased in the ipsilateral basal ganglia after ICH or iron injection. Lipocalin-2-positive cells were astrocytes, microglia, neurons, and endothelial cells. Intracerebral hemorrhage resulted in a significant increase in ferritin expression in the ipsilateral basal ganglia. Compared with WT mice, ICH caused less ferritin upregulation, microglia activation, brain swelling, brain atrophy, and neurologic deficits in LCN2(-/-) mice (P < 0.05). The size of the lesion induced by FeCl2 injection as well as the degree of brain swelling and blood-brain barrier disruption were also less in LCN2(-/-) mice (P < 0.05). These results suggest a role of LCN2 in enhancing brain injury and iron toxicity after ICH.