Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke
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RESEARCH
Open Access
Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke Raquel Rodríguez-González1, Tomás Sobrino1, Manuel Rodríguez-Yáñez1, Mónica Millán2, David Brea1, Elena Miranda3, Octavio Moldes1, Juan Pérez4, David A Lomas3, Rogelio Leira1, Antoni Dávalos2 and José Castillo1*
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 2 as poor outcome.
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Neuroimaging variables
CT scans were carried out on admission and between days 4 and 7. Infarct volume was calculated in the second CT by using the formula 0.5 × a × b × c, where a and b are the largest perpendicular diameters, and c is the number of 1-cm thick sections that contain the lesion. All neuroimaging evaluations were made by the same neuroradiologist who had no knowledge of the patients’ clinical and laboratory results. Laboratory determinations
Serum glucose, platelet count and coagulation tests were assessed in a central laboratory. Blood samples, drawn from all patients on admission, at 24 ± 6 and 72 ± 24 hours, were collected in glass chemistry test tubes, centrifuged at 3000 xg for 10 minutes, and serum immediately frozen and stored at -80°C until analysis. Glutamate levels, as a biomarker of excitotoxicity, were determined by HPLC, using the Waters Pico Tag ® Chemistry Package for HPLC amino acids analysis. IL-6 and ICAM-1, as indexes of inflammatory response, were determined by IMMULITE 1000 System (Siemens) and a commercially available sandwich en
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