Metalloproteinase and stroke infarct size: role for anti-inflammatory treatment?
Anna Morancho1, Anna Rosell, Lidia García-Bonilla
1Neurovascular Research Laboratory, Neurology Department, Hospital Universitari Vall d'Hebron, Institut de Recerca, Universitat Autònoma de Barcelona, Spain.
Abstract:
Deregulation of matrix metalloproteinases (MMPs), the largest class of human proteases, has been implicated in brain damage in both animal and human studies. Some MMPs are elevated after stroke (both in plasma and in brain tissue), and their expression is enhanced by t-PA during thrombolysis related to hemorrhagic transformation events. Although the exact cellular source of MMPs remains unknown, brain endothelium, astrocytes, neurons, and inflammatory-activated cells, such as neutrophils, may release MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, and/or MMP-13. Neurovascular perturbations occurring after stroke lead to blood-brain barrier leakage, edema, hemorrhage, leukocyte infiltration, and progressive inflammatory reactions to brain injury over hours or even days after the initial stroke. Synthesized MMP inhibitors and several compounds used for stroke secondary prevention, such as anti-inflammatory drugs, might decrease MMPs and improve the acute treatment of human brain ischemia without compromising the beneficial effects of matrix plasticity during stroke recovery.
Insights
Matrix metalloproteinases (MMPs) play a role in brain damage after stroke. Inhibiting MMPs may improve acute stroke treatment while preserving recovery benefits.
Area of Science:
- Biochemistry
- Neuroscience
- Pathology
Background:
- Matrix metalloproteinases (MMPs) are key proteases implicated in brain damage.
- Elevated MMP levels are observed in brain tissue and plasma post-stroke.
- MMP expression can be enhanced by tissue plasminogen activator (t-PA) during thrombolysis.
Purpose of the Study:
- To investigate the role of MMPs in stroke-related brain injury.
- To explore potential therapeutic strategies targeting MMPs for acute ischemic stroke treatment.
Main Methods:
- Review of animal and human studies on MMPs in stroke.
- Analysis of cellular sources of MMPs in the brain.
- Examination of neurovascular perturbations and inflammatory responses post-stroke.
Main Results:
- MMPs contribute to neurovascular damage, including blood-brain barrier leakage, edema, and hemorrhage.
- Potential cellular sources include endothelium, astrocytes, neurons, and inflammatory cells.
- MMPs are implicated in progressive inflammatory reactions following ischemic events.
Conclusions:
- MMPs are critical mediators of brain damage in stroke.
- MMP inhibitors and anti-inflammatory drugs show promise for acute stroke treatment.
- Therapeutic strategies should balance MMP inhibition for acute care with preservation of matrix plasticity for recovery.
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