Abstract

Objective: To assess the relationship between matrix metalloproteinase 9 (MMP-9), a proteolytic enzyme involved in the breakdown of the blood-brain barrier, and infarct growth and hemorrhagic transformation in acute ischemic stroke (AIS) with large vessel occlusion (LVO) in the era of mechanical thrombectomy (MT) using the kinetics of MMP-9 and sequential magnetic resonance imaging (MRI).Methods: HIBISCUS-STROKE is a cohort study including AIS patients with LVO treated with MT following admission MRI. Patients underwent sequential assessment of MMP-9, follow-up CT at day 1, and MRI at day 6. The CT scan at day 1 classified any hemorrhagic transformation according to the European Co-operative Acute Stroke Study-II (ECASS II) classification. Infarct growth was defined as the difference between final Fluid-Attenuated Inversion Recovery volume and baseline diffusion-weighted imaging volume. Conditional logistic regression analyses were adjusted for main confounding variables including reperfusion status.Results: One hundred and forty-eight patients represent the study population. A high MMP-9 level at 6 h from admission (H6) (p = 0.02), a high glucose level (p = 0.01), a high temperature (p = 0.04), and lack of reperfusion (p = 0.02) were associated with infarct growth. A high MMP-9 level at H6 (p = 0.03), a high glucose level (p = 0.03) and a long delay from symptom onset to groin puncture (p = 0.01) were associated with hemorrhagic transformation.Conclusions: In this MT cohort study, MMP-9 level at H6 predicts infarct growth and hemorrhagic transformation.

Highlights

  • Ischemia-reperfusion injury in stroke is defined as a biochemical cascade causing a deterioration of ischemic brain tissue that parallels and antagonizes the beneficial effect of reperfusion [1]

  • HIBISCUS-STROKE is a cohort study including acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) treated with mechanical thrombectomy (MT) following admission magnetic resonance imaging (MRI)

  • HIBISCUS-STROKE is an ongoing cohort study including all patients admitted since October 2016 in the Lyon Stroke Department for an acute ischemic stroke (AIS) with large vessel occlusion (LVO) treated either within 0–6 h or 6–24 h time window with MT following brain magnetic resonance imaging (MRI) assessment

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Summary

Introduction

Ischemia-reperfusion injury in stroke is defined as a biochemical cascade causing a deterioration of ischemic brain tissue that parallels and antagonizes the beneficial effect of reperfusion [1]. The increase of BBB permeability is mediated by activation of matrix metalloproteinase (MMP), and especially MMP-9 [2, 3]. Since restoration of the blood supply following MT might be more abrupt and potentially cause greater BBB damage despite a timely and successful reperfusion, an appropriate assessment of MMP-9 activity in this setting may provide additional insight into reperfusion injury related to MT [13]. We sought to determine whether early MMP-9 level is associated with infarct growth and hemorrhagic transformation. For this purpose, a sequential assessment of MMP-9 and ischemic damage using MRI was implemented in the setting of MT

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