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Thesis fall 2015-2-whc-edit-8.pdf (3.09 MB)

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The role of lipocalin-2 in stroke reperfusion injury

Wang, Guona
http://rave.ohiolink.edu/etdc/view?acc_num=kent1448895817

Abstract Details

2015, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Guona Wang, Ph.D., December 2015 Biomedical Science THE ROLE OF LIPOCALIN-2 IN STROKE-REPERFUSION INJURY (107 pages) Dissertation Advisor: Wen-Hai Chou Thrombolysis remains the only effective therapy to reverse acute ischemic stroke. However, delayed treatment may cause serious complications including hemorrhagic transformation and reperfusion injury. The level of lipocalin-2 (LCN2) is elevated in the plasma of ischemic stroke patients, but its role in stroke is unknown. Here we show that LCN2 was acutely induced in mice after ischemic stroke and is an important mediator of reperfusion injury. Increased levels of LCN2 were observed in mouse serum as early as one hour after transient middle cerebral artery occlusion (tMCAO), reaching peak levels at 23 hours. LCN2 was also detected in neutrophils infiltrating into the ipsilateral hemisphere, as well as a subset of reactive astrocytes after tMCAO, but not in neurons and microglia. Stroke injury, neurological deficits and infiltration of immune cells were markedly diminished in LCN2 null mice after tMCAO, but not after permanent MCAO (pMCAO). In vitro, recombinant LCN2 protein induced apoptosis in primary cultured neurons in a dose-dependent manner. Brain injury, neurological deficits, blood brain barrier leakage and immune cell infiltration were significantly reduced in mice with anti-LCN2 antibody treatment. Our results demonstrate that LCN2 is a neurotoxic factor secreted rapidly in response to cerebral ischemia, suggesting its potential usage as an early stroke biomarker and a novel therapeutic target to reduce stroke-reperfusion injury.
Wen-Hai Chou (Advisor)
Srinivasan Vijayaraghavan (Committee Member)
Gail Fraizer (Committee Member)
Werner Geldenhuys (Committee Member)
Joel Hughes (Other)
107 p.
Biomedical Research

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Citations

  • Wang, G. (2015). The role of lipocalin-2 in stroke reperfusion injury [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1448895817

    APA Style (7th edition)

  • Wang, Guona. The role of lipocalin-2 in stroke reperfusion injury. 2015. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1448895817.

    MLA Style (8th edition)

  • Wang, Guona. "The role of lipocalin-2 in stroke reperfusion injury." Doctoral dissertation, Kent State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=kent1448895817

    Chicago Manual of Style (17th edition)

kent1448895817
287
© 2015, some rights reserved.Creative Commons License The role of lipocalin-2 in stroke reperfusion injury by Guona Wang is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Kent State University and OhioLINK.