title: Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke.
abstract: BACKGROUND
  Neuroserpin has shown neuroprotective effects in animal models of cerebral ischemia and has been associated with functional outcome after ischemic stroke. Our aim was to study whether neuroserpin serum levels could be associated to biomarkers of excitotoxicity, inflammation and blood brain barrier disruption.
  
  
  METHODS
  We prospectively included 129 patients with ischemic stroke (58.1% male; mean age, 72.4 ± 9.6 years) not treated with tPA within 12 hours (h) of symptoms onset (mean time, 4.7 ± 2.1 h). Poor functional outcome at 3 months was considered as a modified Rankin scale score >2. Serum levels of neuroserpin, Interleukin 6 (IL-6), Intercellular adhesion molecule-1 (ICAM-1), active Matrix metalloproteinase 9 (MMP-9), and cellular fibronectin (cFn) (determined by ELISA) and glutamate (determined by HPLC) were measured on admission, 24 and 72 h. The main variable was considered the decrease of neuroserpin levels within the first 24 h. ROC analysis was used to select the best predictive value for neuroserpin to predict poor functional outcome due to a lack of linearity.
  
  
  RESULTS
  The decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels at 24 hours of glutamate (r = -0.642), IL-6 (r = -0.678), ICAM-1 (r = -0.345), MMP-9 (r = -0.554) and cFn (r = -0.703) (all P < 0.0001). In the multivariate analysis, serum levels of glutamate (OR, 1.04; CI95%, 1.01-1.06, p = 0.001); IL-6 (OR, 1.4; CI95%, 1.1-1.7, p = 0.001); and cFn (OR, 1.3; CI95%, 1.1-1.6, p = 0.002) were independently associated with a decrease of neuroserpin levels <70 ng/mL at 24 h after adjusting for confounding factors.
  
  
  CONCLUSIONS
  These findings suggest that neuroprotective properties of neuroserpin may be related to the inhibition of excitotoxicity, inflammation, as well as blood brain barrier disruption that occur after acute ischemic stroke.
authors.affiliation: Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Rodríguez-González
authors.forename: Tomás
authors.initials: T
authors.lastname: Sobrino
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Yáñez
authors.forename: Mónica
authors.initials: M
authors.lastname: Millán
authors.forename: David
authors.initials: D
authors.lastname: Brea
authors.forename: Elena
authors.initials: E
authors.lastname: Miranda
authors.forename: Octavio
authors.initials: O
authors.lastname: Moldes
authors.forename: Juan
authors.initials: J
authors.lastname: Pérez
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Rogelio
authors.initials: R
authors.lastname: Leira
authors.forename: Antoni
authors.initials: A
authors.lastname: Dávalos
authors.forename: José
authors.initials: J
authors.lastname: Castillo
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000097:blood* / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D009479:Neuropeptides / Q000097:blood*; D016017:Odds Ratio; D015843:Serpins / Q000097:blood*; D020521:Stroke / Q000097:blood* / Q000150:complications*; D013997:Time Factors; D000097522:Neuroserpin
chemical_list: D015415:Biomarkers; D009479:Neuropeptides; D015843:Serpins; D000097522:Neuroserpin