Inflammation biomarkers in the intracranial blood are associated with outcome in patients with ischemic stroke
Cyril Dargazanli, Marine Blaquière, Marinette Moynier, Frédéric de Bock, Julien Labreuche, Adrien ter Schiphorst, Imad Derraz, Răzvan Alexandru Radu, Grégory Gascou, Pierre-Henri Lefèvre, Francesca Rapido, Julien Fendeleur, Caroline Arquizan, Romain Bourcier, Philippe Marin, Paolo Machi, Fédérico Cagnazzo, Christophe Hirtz, Vincent Costalat, Vincent Costalat, Nicola Marchi, Nicola Marchi
Abstract
BACKGROUND: Performing endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) allows a port of entry for intracranial biological sampling. OBJECTIVE: To test the hypothesis that specific immune players are molecular contributors to disease, outcome biomarkers, and potential targets for modifying AIS . METHODS: We examined 75 subjects presenting with large vessel occlusion of the anterior circulation and undergoing EVT. Intracranial blood samples were obtained by microcatheter aspiration, as positioned for stent deployment. Peripheral blood samples were collected from the femoral artery. Plasma samples were quality controlled by electrophoresis and analyzed using a Mesoscale multiplex for targeted inflammatory and vascular factors. RESULTS: We measured 37 protein biomarkers in our sample cohort. Through multivariate analysis, adjusted for age, intravenous thrombolysis, pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT scores, we found that post-clot blood levels of interleukin-6 (IL-6) were significantly correlated (adjusted P value <0.05) with disability assessed by the modified Rankin Scale (mRS) score at 90 days, with medium effect size. Chemokine (C-C) ligand 17 CCL17/TARC levels were inversely correlated with the mRS score. Examination of peripheral blood showed that these correlations did not reach statistical significance after correction. Intracranial biomarker IL-6 level was specifically associated with a lower likelihood of favorable outcome, defined as a mRS score of 0-2. CONCLUSIONS: Our findings show a signature of blood inflammatory factors at the cerebrovascular occlusion site. The correlations between these acute-stage biomarkers and mRS score outcome support an avenue for add-on and localized immune modulatory strategies in AIS.