title: Lipocalin-2 as an Infection-Related Biomarker to Predict Clinical Outcome in Ischemic Stroke.
abstract: From previous data in animal models of cerebral ischemia, lipocalin-2 (LCN2), a protein related to neutrophil function and cellular iron homeostasis, is supposed to have a value as a biomarker in ischemic stroke patients. Therefore, we examined LCN2 expression in the ischemic brain in an animal model and measured plasma levels of LCN2 in ischemic stroke patients.
  
  
  
  In the mouse model of transient middle cerebral artery occlusion (tMCAO), LCN2 expression in the brain was analyzed by immunohistochemistry and correlated to cellular nonheme iron deposition up to 42 days after tMCAO. In human stroke patients, plasma levels of LCN2 were determined one week after ischemic stroke. In addition to established predictive parameters such as age, National Institutes of Health Stroke Scale and thrombolytic therapy, LCN2 was included into linear logistic regression modeling to predict clinical outcome at 90 days after stroke.
  
  
  
  Immunohistochemistry revealed expression of LCN2 in the mouse brain already at one day following tMCAO, and the amount of LCN2 subsequently increased with a maximum at 2 weeks after tMCAO. Accumulation of cellular nonheme iron was detectable one week post tMCAO and continued to increase. In ischemic stroke patients, higher plasma levels of LCN2 were associated with a worse clinical outcome at 90 days and with the occurrence of post-stroke infections.
  
  
  
  LCN2 is expressed in the ischemic brain after temporary experimental ischemia and paralleled by the accumulation of cellular nonheme iron. Plasma levels of LCN2 measured in patients one week after ischemic stroke contribute to the prediction of clinical outcome at 90 days and reflect the systemic response to post-stroke infections.
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Hochmeister
authors.affiliation: Department of Experimental Neurology, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Odilo
authors.initials: O
authors.lastname: Engel
authors.affiliation: Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Milena Z
authors.initials: MZ
authors.lastname: Adzemovic
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.|University of Applied Sciences Wiener Neustadt, Wiener Neustadt, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pekar
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.|Department of Neurosurgery, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Kendlbacher
authors.affiliation: Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Manuel
authors.initials: M
authors.lastname: Zeitelhofer
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Haindl
authors.affiliation: Department of Experimental Neurology, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meisel
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Seifert-Held
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D000071068:Lipocalin-2 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D015415:Biomarkers; D000071068:Lipocalin-2