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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Cheng Y, Xi G, Jin H, Keep RF, Feng J, Hua Y (2014) Thrombin-induced cerebral hemorrhage: role of protease-activated receptor-1. Transl Stroke Res 5:472–475
Devireddy LR, Gazin C, Zhu X, Green MR (2005) A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell 123:1293–1305
Dong M, Xi G, Keep RF, Hua Y (2013) Role of iron in brain lipocalin 2 upregulation after intracerebral hemorrhage in rats. Brain Res 1505:86–92
Egashira Y, Hua Y, Keep RF, Xi G (2014) Acute white matter injury after experimental subarachnoid hemorrhage: potential role of lipocalin 2. Stroke 45:2141–2143
Glushakova OY, Johnson D, Hayes RL (2014) Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage. J Neurotrauma 31:1180–1193
Jin H, Xi G, Keep RF, Wu J, Hua Y (2013) DARPP-32 to quantify intracerebral hemorrhage-induced neuronal death in basal ganglia. Transl Stroke Res 4:130–134
Jin M, Kim JH, Jang E, Lee YM, Soo Han H, Woo DK, Park DH, Kook H, Suk K (2014) Lipocalin-2 deficiency attenuates neuroinflammation and brain injury after transient middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab 34:1306–1314
Kamii H, Kato I, Kinouchi H, Chan PH, Epstein CJ, Akabane A, Okamoto H, Yoshimoto T (1999) Amelioration of vasospasm after subarachnoid hemorrhage in transgenic mice overexpressing CuZn-superoxide dismutase. Stroke 30:867–871; discussion 872
Keep RF, Xiang J, Ennis SR, Andjelkovic A, Hua Y, Xi G, Hoff JT (2008) Blood-brain barrier function in intracerebral hemorrhage. Acta Neurochir Suppl 105:73–77
Lee JY, Keep RF, He Y, Sagher O, Hua Y, Xi G (2010) Hemoglobin and iron handling in brain after subarachnoid hemorrhage and the effect of deferoxamine on early brain injury. J Cereb Blood Flow Metab 30:1793–1803
Rathore KI, Berard JL, Redensek A, Chierzi S, Lopez-Vales R, Santos M, Akira S, David S (2011) Lipocalin 2 plays an immunomodulatory role and has detrimental effects after spinal cord injury. J Neurosci 31:13412–13419
Seo JH, Miyamoto N, Hayakawa K, Pham LD, Maki T, Ayata C, Kim KW, Lo EH, Arai K (2013) Oligodendrocyte precursors induce early blood-brain barrier opening after white matter injury. J Clin Invest 123:782–786
Zhao J, Chen Z, Xi G, Keep RF, Hua Y (2014) Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats. Transl Stroke Res 5:586–594
Acknowledgment
This study was supported by grants NS-073595, NS-079157, and NS-084049 from the National Institutes of Health (NIH), 973 Program-2014CB541600, and Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Egashira, Y., Hua, Y., Keep, R.F., Iwama, T., Xi, G. (2016). Lipocalin 2 and Blood-Brain Barrier Disruption in White Matter after Experimental Subarachnoid Hemorrhage. In: Applegate, R., Chen, G., Feng, H., Zhang, J. (eds) Brain Edema XVI. Acta Neurochirurgica Supplement, vol 121. Springer, Cham. https://doi.org/10.1007/978-3-319-18497-5_23
Download citation
DOI: https://doi.org/10.1007/978-3-319-18497-5_23
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-18496-8
Online ISBN: 978-3-319-18497-5
eBook Packages: MedicineMedicine (R0)