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Increased brain expression of matrix metalloproteinase-9 after ischemic and hemorrhagic human stroke
Anna Rosell1, Arantxa Ortega-Aznar, José Alvarez-Sabín
1Department of Neurology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Background And Purpose:
Abnormal expression of some matrix metalloproteinases (MMP) has shown to play a deleterious role in brain injury in experimental models of cerebral ischemia. We aimed to investigate MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in brain parenchyma in both ischemic and hemorrhagic strokes.
Methods:
Postmortem fresh brain tissue from 6 ischemic and 8 hemorrhagic stroke patients was obtained within the first 6 hours after death. Finally, 78 brain tissue samples from different areas (infarct, peri-infarct, perihematoma and contralateral hemisphere) were studied. To quantify gelatinase content we performed gelatin zymograms that were confirmed by Western Blot Analysis, immunohistochemistry to localize MMP source, and in situ zymography to detect gelatinase activity.
Results:
Among ischemic cases, gelatin zymography showed increased MMP-9 content in infarct core although peri-infarct tissue presented also higher levels than contralateral hemisphere (P<0.0001 and P=0.042, respectively). Within infarct core, MMP-9 was mainly located around blood vessels, associated to neutrophil infiltration and activated microglial cells. In peri-infarct areas the major source of MMP-9 were microglial cells. Tissue around intracranial hemorrhage also displayed higher MMP-9 levels than contralateral hemisphere (P=0.008) in close relationship with glial cells. MMP-2 was constitutively expressed and remained invariable in different brain areas.
Conclusions:
Our results demonstrate in situ higher levels of MMP-9 in human brain tissue after ischemic and hemorrhagic stroke, suggesting a contribution of MMP-9 to ischemic brain injury and perihematoma edema.
Insights
Matrix metalloproteinase-9 (MMP-9) levels are elevated in human brain tissue following both ischemic and hemorrhagic strokes. This suggests MMP-9 contributes to brain damage and swelling after stroke.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Matrix metalloproteinases (MMPs) are implicated in brain injury.
- Abnormal MMP expression is linked to experimental cerebral ischemia.
Purpose of the Study:
- Investigate matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in human ischemic and hemorrhagic stroke brain tissue.
- Determine the role of MMPs in stroke pathogenesis.
Main Methods:
- Analyzed postmortem brain tissue from ischemic and hemorrhagic stroke patients.
- Quantified gelatinase content using gelatin zymograms, Western Blot, immunohistochemistry, and in situ zymography.
- Examined infarct, peri-infarct, perihematoma, and contralateral hemisphere samples.
Main Results:
- MMP-9 levels were significantly increased in infarct cores and peri-infarct areas of ischemic stroke.
- MMP-9 was elevated around blood vessels and associated with neutrophils and microglia in infarcts.
- MMP-9 was also higher in tissues surrounding hemorrhagic stroke, linked to glial cells.
- MMP-2 expression remained constant across all studied areas.
Conclusions:
- Elevated MMP-9 levels are present in human ischemic and hemorrhagic stroke tissue.
- MMP-9 likely contributes to ischemic brain injury and perihematoma edema.
- Findings highlight MMP-9 as a potential therapeutic target in stroke.
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01:15Ischemic Stroke ll: Pathophysiology
01:29Hemorrhagic Stroke ll: Pathophysiology