Immune Cells Invade the Collateral Circulation during Human Stroke: Prospective Replication and Extension.

Marc Strinitz,Marius L Vogt,Hermann Neugebauer,Guido Stoll,Alexander G März,Mirko Pham,Jörn Feick,Franziska Weidner,Michael K Schuhmann,Alexander M Kollikowski,Fabian Essig

doi:10.3390/ijms22179161

Marc Strinitz, Marius L Vogt + Show 9 more

Open Access

https://doi.org/10.3390/ijms22179161

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Abstract

It remains unclear if principal components of the local cerebral stroke immune response can be reliably and reproducibly observed in patients with acute large-vessel-occlusion (LVO) stroke. We prospectively studied a large independent cohort of n = 318 consecutive LVO stroke patients undergoing mechanical thrombectomy during which cerebral blood samples from within the occluded anterior circulation and systemic control samples from the ipsilateral cervical internal carotid artery were obtained. An extensive protocol was applied to homogenize the patient cohort and to standardize the procedural steps of endovascular sample collection, sample processing, and laboratory analyses. N = 58 patients met all inclusion criteria. (1) Mean total leukocyte counts were significantly higher within the occluded ischemic cerebral vasculature (I) vs. intraindividual systemic controls (S): +9.6%, I: 8114/µL ± 529 vs. S: 7406/µL ± 468, p = 0.0125. (2) This increase was driven by neutrophils: +12.1%, I: 7197/µL ± 510 vs. S: 6420/µL ± 438, p = 0.0022. Leukocyte influx was associated with (3) reduced retrograde collateral flow (R2 = 0.09696, p = 0.0373) and (4) greater infarct extent (R2 = 0.08382, p = 0.032). Despite LVO, leukocytes invade the occluded territory via retrograde collateral pathways early during ischemia, likely compromising cerebral hemodynamics and tissue integrity. This inflammatory response can be reliably observed in human stroke by harvesting immune cells from the occluded cerebral vascular compartment.

Highlights

The cumulative incidence of cerebrovascular diseases is considerable in high-income countries (218 per 100,000 in men and 127 per 100,000 in women, respectively) and has reached epidemic levels in low to middle-income countries [1,2]
In acute ischemic stroke (AIS), the immune system exerts a strong and early inflammatory response, which is directed at the ischemic brain [5,6]
Discussion compartment and which is directed at the ischemic brain region [22,23]

Summary

Introduction

The cumulative incidence of cerebrovascular diseases is considerable in high-income countries (218 (95% CI 214–221) per 100,000 in men and 127 (95% CI 125–128) per 100,000 in women, respectively) and has reached epidemic levels in low to middle-income countries [1,2]. The ischemic cerebral vasculature of acute stroke patients has become accessible for investigation during mechanical thrombectomy (MT), while, importantly, recanalization still has not taken place: We and few other groups established the method of blood aspiration from within the ischemic cerebral vasculature during MT, which is performed with a distally placed microcatheter at the end of the occlusion phase immediately before therapeutic recanalization is achieved more proximally through stent-embolus-retrieval [17,18,19] In principle, this method can expose local pathophysiology for scientific observation if patient-related, interventional, and laboratory confounders are controlled by protocol [17,20,21]. The reproducibility and consistency of observations made by this approach remain unclear

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