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Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke.

Rodríguez-González R, Sobrino T, Rodríguez-Yáñez M, Millán M, Brea D, Miranda E, Moldes O, Pérez J, Lomas DA, Leira R, Dávalos A, Castillo J - J Transl Med (2011)

Bottom Line: The main variable was considered the decrease of neuroserpin levels within the first 24 h.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain.

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.

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Significant correlations between neuroserpin decrease within the first 24 hours and levels of molecular markers of brain damage at 24 hours.
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Figure 1: Significant correlations between neuroserpin decrease within the first 24 hours and levels of molecular markers of brain damage at 24 hours.

Mentions: We evaluated the relationship between neuroserpin levels and brain injury biomarkers on admission as well as between neuroserpin decrease within the first 24 hours and biomarkers serum levels at 24 hours from stroke onset. We did not find a significant correlation between neuroserpin serum levels on admission and glutamate (r = -0.138, p = 0.133), IL-6 (r = -0.062, p = 0.485), ICAM-1 (r = 0.004, p = 0.964), active MMP-9 (r = 0.143, p = 0.224) or cFn (r = -0.139, p = 0.117). However, the decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels of brain injury biomarkers at 24 hours: glutamate (r = -0.642), IL-6 (r = -0.678), ICAM-1 (r = -0.345), active MMP-9 (r = -0.554), cFn (r = -0.703), (all P < 0.0001) (Figure 1).


Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke.

Rodríguez-González R, Sobrino T, Rodríguez-Yáñez M, Millán M, Brea D, Miranda E, Moldes O, Pérez J, Lomas DA, Leira R, Dávalos A, Castillo J - J Transl Med (2011)

Significant correlations between neuroserpin decrease within the first 24 hours and levels of molecular markers of brain damage at 24 hours.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3113955&req=5

Figure 1: Significant correlations between neuroserpin decrease within the first 24 hours and levels of molecular markers of brain damage at 24 hours.
Mentions: We evaluated the relationship between neuroserpin levels and brain injury biomarkers on admission as well as between neuroserpin decrease within the first 24 hours and biomarkers serum levels at 24 hours from stroke onset. We did not find a significant correlation between neuroserpin serum levels on admission and glutamate (r = -0.138, p = 0.133), IL-6 (r = -0.062, p = 0.485), ICAM-1 (r = 0.004, p = 0.964), active MMP-9 (r = 0.143, p = 0.224) or cFn (r = -0.139, p = 0.117). However, the decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels of brain injury biomarkers at 24 hours: glutamate (r = -0.642), IL-6 (r = -0.678), ICAM-1 (r = -0.345), active MMP-9 (r = -0.554), cFn (r = -0.703), (all P < 0.0001) (Figure 1).

Bottom Line: The main variable was considered the decrease of neuroserpin levels within the first 24 h.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain.

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.

Show MeSH
Related in: MedlinePlus