Local leukocyte invasion during hyperacute human ischemic stroke.

OBJECTIVE: Bridging the gap between experimental stroke and patients by ischemic blood probing during the hyperacute stage of vascular occlusion is crucial to assess the role of inflammation in human stroke and for the development of adjunct treatments beyond recanalization.

METHODS: We prospectively observed 151 consecutive ischemic stroke patients with embolic large vessel occlusion of the anterior circulation who underwent mechanical thrombectomy. In all these patients, we attempted microcatheter aspiration of three different arterial blood samples 1) within the core of the occluded vascular compartment, controlled by 2) carotid and 3) femoral samples obtained under physiological flow conditions. Subsequent laboratory analyses comprised leukocyte counting and differentiation, platelet counting, and the quantification of 13 proinflammatory human chemokines/cytokines.

RESULTS: 40 patients meeting all clinical, imaging, interventional and laboratory inclusion criteria could be analyzed, showing that: (1) The total number of leukocytes significantly increased under the occlusion condition. (2) This increase was predominantly driven by neutrophils. Significant increases were also apparent for (3) lymphocytes and (4) monocytes, accompanied by locally elevated plasma levels of the (5) T-cell chemoattractant CXCL-11. Finally, we found evidence that (6) short-term clinical outcome (NIHSS at 72h) was negatively associated with neutrophil accumulation.

INTERPRETATION: We provide the first direct human evidence that neutrophils, lymphocytes and monocytes, accompanied by specific chemokine upregulation, accumulate in the ischemic vasculature during hyperacute stroke and may affect outcome. These findings strongly support experimental evidence that immune cells contribute to acute ischemic brain damage and indicate that ischemic inflammation initiates already during vascular occlusion. This article is protected by copyright. All rights reserved.