Abstract
BackgroundNeuroserpin 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.MethodsWe 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.ResultsThe 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.ConclusionsThese 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.
Highlights
Neuroserpin has shown neuroprotective effects in animal models of cerebral ischemia and has been associated with functional outcome after ischemic stroke
Our analysis focused on those molecular markers of brain injury which were positively associated with a decrease in neuroserpin levels
The results of the present study show a significant association between neuroserpin decrease < 70 ng/mL and serum levels of brain injury biomarkers at 24 hours, which remained independent for glutamate, IL-6 and cellular fibronectin (cFn) after adjusting for confounding factors
Summary
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. It is known that tPA is able to promote neuronal injury in the brain parenchyma by enhancing different mechanisms, such as the activation of microglia [1] as well as affecting neuronal N-methyl-D-aspartate (NMDA) receptor-mediated signalling [2]. This leads to an association between neuroserpin serum levels and functional outcome in patients with ischemic stroke has recently been reported [6]. Glutamate was measured as a marker of excitotoxic damage, interleukin-6 (IL-6) and Intercellular Adhesion Molecule-1 (ICAM-1) as markers of inflammatory response, and matrix metalloproteinase 9 (MMP-9) and cellular fibronectin (cFn) as markers of blood brain barrier disruption after ischemic stroke
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