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Analysis of the association of MPO and MMP-9 with stroke severity and outcome: Cohort study
Ilaria Maestrini1, Madjid Tagzirt1, Sophie Gautier1
1From the Departments of Neurology (I.M., A.-M.M., C.C., D.L.) and Medical Pharmacology (S.G., R.B.), Degenerative and Vascular Cognitive Disorders, University Hospital CHU Lille, Inserm U1171, University of Lille, France; Department of Human Neurosciences (I.M.), "Sapienza" University of Rome, Italy; and European Genomic Institute for Diabetes (M.T., A.D., S.S., A.T., E.V., B.S.), University Hospital CHU Lille, Inserm U1011, Institut Pasteur of Lille, University of Lille, France.
Objective:
In acute cerebral ischemia, circulating neutrophil count and neutrophil-to-lymphocyte ratio (NLR) are positively associated with stroke severity and worse outcomes. Mediators of this effect are unknown. We aimed to investigate (1) the relationship between plasma matrix metalloproteinase-9 (MMP-9) and myeloperoxidase (MPO) concentrations with stroke severity and outcome and (2) MMP-9 and MPO release after ex vivo stimulation of neutrophils by recombinant tissue plasminogen activator (rtPA).
Methods:
We analyzed data collected in 255 patients with supratentorial cerebral infarcts recruited within 48 hours of symptoms onset irrespective of rtPA treatment. The endpoints were excellent outcome (modified Rankin Scale score 0-1), symptomatic intracerebral hemorrhage (European Cooperative Acute Stroke Study-II definition), and death at 3 months. The role of rtPA treatment on peripheral neutrophil degranulation was investigated in 18 patients within 4.5 hours and after 72 hours.
Results:
Neutrophil counts, NLR, and MPO plasma concentrations, but not MMP-9, were positively correlated with stroke severity. Higher neutrophil counts and NLR were independently associated with worse outcomes and higher mortality rates at month 3. Higher MPO plasma concentrations, but not MMP-9, were associated with worse outcome. Neutrophil-derived MMP-9, after ex vivo rtPA stimulation, but not MPO, were higher after 72 hours in patients treated by IV rtPA but not associated with hemorrhagic transformation.
Conclusions:
Neutrophil counts, NLR, and MPO plasma concentrations are associated with worse outcome in patients with acute cerebral ischemia, in contrast to MMP-9. Further investigations are needed to deepen our knowledge on MPO's role in the deleterious effect of neutrophils because it could represent a potential therapeutic target.
Insights
Higher neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), and myeloperoxidase (MPO) are linked to worse outcomes in acute cerebral ischemia. Matrix metalloproteinase-9 (MMP-9) did not show this association.
Area of Science:
- Neurology
- Immunology
- Biochemistry
Background:
- Acute cerebral ischemia is associated with elevated circulating neutrophil counts and neutrophil-to-lymphocyte ratio (NLR).
- The specific mediators linking neutrophils to stroke severity and outcomes remain unclear.
- Investigating plasma matrix metalloproteinase-9 (MMP-9) and myeloperoxidase (MPO) as potential mediators is crucial.
Purpose of the Study:
- To determine the relationship between plasma MMP-9 and MPO concentrations and stroke severity and outcomes.
- To examine MMP-9 and MPO release from neutrophils after ex vivo stimulation with recombinant tissue plasminogen activator (rtPA).
Main Methods:
- Analysis of data from 255 patients with supratentorial cerebral infarcts within 48 hours of symptom onset.
- Assessment of outcomes including excellent outcome (modified Rankin Scale 0-1), symptomatic intracerebral hemorrhage, and 3-month mortality.
- Investigation of rtPA's effect on peripheral neutrophil degranulation in 18 patients at 4.5 and 72 hours.
Main Results:
- Neutrophil counts, NLR, and MPO plasma concentrations correlated positively with stroke severity.
- Higher neutrophil counts and NLR were independently linked to worse outcomes and increased 3-month mortality.
- Higher MPO concentrations were associated with worse outcomes, while MMP-9 showed no significant association with severity or outcome.
Conclusions:
- Neutrophil counts, NLR, and MPO are associated with adverse outcomes in acute cerebral ischemia, unlike MMP-9.
- Myeloperoxidase (MPO) warrants further investigation as a potential therapeutic target due to its association with neutrophil-driven deleterious effects.
- Understanding MPO's role could lead to novel therapeutic strategies for acute ischemic stroke.
