Matrix Metalloproteinase-9 Relationship With Infarct Growth and Hemorrhagic Transformation in the Era of Thrombectomy

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.

Association of Matrix Metalloproteinase 9 and Cellular Fibronectin and Outcome in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

“…Two articles involved the same participants ( 9 , 32 ), so we included data only from the more recent publication ( 32 ). In the end, 28 articles ( 6 , 8 , 15 , 19 , 27 , 32 – 54 ) involving 7,239 patients were included in the review ( Table 1 ).…”

“…One article was designed as a case-control study ( 36 ), and the others were cohort studies. Most studies enrolled patients with all types of acute ischemic stroke, except for three studies including patients without lacunar stroke ( 33 , 34 , 40 ), three studies including patients with cardioembolic stroke involving middle cerebral artery ( 33 – 35 ), and one study including patients with large-vessel occlusion treated with mechanical thrombectomy ( 54 ). Treatment with thrombolysis varied across studies: 10 studies included patients treated with thrombolysis ( 15 , 27 , 32 , 34 – 36 , 38 , 42 , 48 , 54 ), four studies had some patients who received thrombolysis ( 19 , 39 – 41 ), and the remaining 12 studies included patients who did not receive thrombolytic treatment.…”

Structural and Functional Remodeling of the Brain Vasculature Following Stroke

“…In this study, MMP-9 levels were assessed to determine whether it correlated with infarct growth and hemorrhagic transformation. The study showed that MMP-9 levels measured 6 h after admission predicted infarct growth and hemorrhagic transformation (Mechtouff et al, 2020).…”

“…MMP-9 is associated with BBB breakdown and subsequent vasogenic edema, and an MMP-9 polymorphism was shown to confer susceptibility to ischemic stroke in a Chinese population (Jiang et al, 2020). HIBISCUS-STROKE is a cohort study including acute ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy following admission magnetic resonance imaging (MRI) (Mechtouff et al, 2020). In this study, MMP-9 levels were assessed to determine whether it correlated with infarct growth and hemorrhagic transformation.…”

“…-VEGF can also increase BBB permeability, which may help peripheral macrophages infiltrate into the brain. Manoonkitiwongsa et al, 2001;Gould et al, 2006;Chen et al, 2013;Fu et al, 2014;Lan et al, 2017;Zhang et al, 2017;Gautam et al, 2020;Mechtouff et al, 2020.…”