Molecular markers are associated with early computed tomography ischemic changes]

Introduction. During brain ischemia, neurotoxicity, neuroinflammation and blood-brain barrier (BBB) disruption mechanisms are involved, leading to necrosis, edema and hemorrhagic transformation. Cranial computed tomography (CT) is the most widely used method in the diagnosis of acute stroke, and its early performance may help in the selection of patients for certain treatments. Our objective is to identify molecular markers of neuroexcitotoxicity, neuroinflammation and BBB disruption in the acute phase of stroke that might be associated with early ischemic CT signs. Methods. 311 patients with ischemic stroke within the first 24 h from symptoms onset were prospectively included. We established tres groups based on the time between symptom onset and hospital arrival: <= 6 h, between 6 and 12 h and > 12 h. Cranial CT was performed at admission to evaluate early ischemic signs according to the Alberta Stroke Program Early CT Score (ASPECTS). Blood samples were taken at admission for the determination of molecular markers of neuroexcitotoxicity (glutamate), neuroinflammation (interleukin [IL]-6) and BBB disruption (metalloproteinase [MMP]-9). Results. Patients with ASPECTS score <= 7 showed a worse early and late prognosis. Glutamate < 134.4 mu M (OR: 9.7; CI 95%: 4.2-22.5; p < 0.001), IL-6 > 15.5 pg/mL (OR: 4.4; CI 95%: 2.1-9.4; p < 0.001) and MMP-9 > 87.2 ng/mL (OR: 18.4; CI 95%: 7.2-47.1; p < 0.001) were associated with ASPECTS score <= 7. In the logistic regression model, only glutamate > 134.4 mu M/l in the first 6 h (OR: 13.2; CI 95%: 5.4-31.3; p < 0.001), IL-6 > 15.5 pg/mL from 6 to 12 h (OR: 10.5; CI 95%: 4.1-26.7; p < 0.001) and MMP-9 > 87.2 ng/ml after 12 h (OR: 24.2; CI 95%: 4.8-50.2; p < 0.001) were independently associated with ASPECTS score <= 7. Conclusions. The ASPECTS score may be considered as a surrogate marker of early neurological deterioration and final infarct volume, and associated with molecular markers of neuroexcitotoxicity, neuroinflammation and BBB disruption.