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Updated: Aug 17, 2026
Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
Published on: May 8, 2017
A matrix metalloproteinase protein array reveals a strong relation between MMP-9 and MMP-13 with diffusion-weighted
Anna Rosell1, José Alvarez-Sabín, Juan F Arenillas
1Neurology Department, Universitat Autònoma de Barcelona, Hospital Vall d'Hebron, Barcelona, Spain.
Background And Purpose:
Matrix metalloproteinases (MMPs) are involved in tissue destruction produced by the neuroinflammatory response that follows ischemic stroke. In the present study we use an MMP array to investigate the blood levels of several MMPs in stroke patients and its relation with brain tissue damage and neurological outcome.
Methods:
Twenty-four patients with middle cerebral artery occlusion who received thrombolytic therapy were included. Blood samples were drawn before tissue plasminogen activator treatment and an MMP array (multiplex enzyme-linked immunosorbent assay [ELISA]) was performed including gelatinases (MMP-2 and MMP-9), collagenases (MMP-1, MMP-8, and MMP-13), stromelysines (MMP-3 and MMP-10), and MMP endogen inhibitors (TIMP-1 and TIMP-2). To assess tissue lesion a serial multimodal MRI study was performed (pretreatment and at 24 hours).
Results:
Neither initial diffusion lesion nor hypoperfused volume was associated with metalloproteinase expression within the first 3 hours after stroke onset. Nevertheless, a strong correlation was found between MMP-9 and MMP-13 with diffusion-weighted image (DWI) lesion expansion (r=0.54, P=0.05 and r=0.60, P=0.017, respectively). Baseline levels of both MMP-9 (OR, 14;95% CI, 1.5 to 131; P=0.019) and MMP-13 (OR, 73; 95% CI, 3.9 to 1388; P=0.004) were independent predictors of final increase in brain infarct volume at 24 hours.
Conclusions:
Our results demonstrate that within the neuroinflammatory response, high levels of MMP-9 and MMP-13 are involved in DWI lesion growth despite thrombolytic therapy, suggesting its ultra-early role in brain injury.
Insights
High levels of matrix metalloproteinases (MMPs), specifically MMP-9 and MMP-13, correlate with increased brain lesion expansion after ischemic stroke. These MMPs are early predictors of infarct volume growth, even with thrombolytic therapy.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Matrix metalloproteinases (MMPs) contribute to tissue damage during the neuroinflammatory response post-ischemic stroke.
- Investigating MMPs' role in stroke is crucial for understanding brain injury progression.
Purpose of the Study:
- To analyze blood levels of various MMPs in stroke patients.
- To determine the relationship between MMP levels, brain tissue damage, and neurological outcomes.
Main Methods:
- Utilized an MMP array (multiplex ELISA) on blood samples from 24 stroke patients before thrombolytic therapy.
- Assessed brain tissue lesion using serial multimodal MRI (Diffusion-weighted imaging).
- Measured gelatinases (MMP-2, MMP-9), collagenases (MMP-1, MMP-8, MMP-13), and inhibitors (TIMP-1, TIMP-2).
Main Results:
- No initial association between early MMP expression and lesion/hypoperfused volume.
- Significant correlation found between MMP-9 and MMP-13 levels and diffusion-weighted image (DWI) lesion expansion.
- Baseline MMP-9 and MMP-13 independently predicted final infarct volume increase at 24 hours.
Conclusions:
- Elevated MMP-9 and MMP-13 levels are implicated in DWI lesion growth during the neuroinflammatory response post-stroke.
- These findings suggest an ultra-early role for MMP-9 and MMP-13 in acute ischemic brain injury progression.
- MMP levels may serve as early biomarkers for stroke lesion development.
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