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Microglial Cell Activation is a Source of Metalloproteinase Generation during Hemorrhagic Transformation
- Source :
- Journal of Cerebral Blood Flow & Metabolism. 32:919-932
- Publication Year :
- 2012
- Publisher :
- SAGE Publications, 2012.
-
Abstract
- Hemorrhage and edema accompany evolving brain tissue injury after ischemic stroke. In patients, these events have been associated with metalloproteinase (MMP)-9 in plasma. Both the causes and cellular sources of MMP-9 generation in this setting have not been defined. MMP-2 and MMP-9 in nonhuman primate tissue in regions of plasma leakage, and primary murine microglia and astrocytes, were assayed by immunocytochemistry, zymography, and real-time RT-PCR. Ischemia-related hemorrhage was associated with microglial activation in vivo, and with the leakage of plasma fibronectin and vitronectin into the surrounding tissue. In strict serum-depleted primary cultures, by zymography, pro-MMP-9 was generated by primary murine microglia when exposed to vitronectin and fibronectin. Protease secretion was enhanced by experimental ischemia (oxygen-glucose deprivation, OGD). Primary astrocytes, on each matrix, generated only pro-MMP-2, which decreased during OGD. Microglia—astrocyte contact enhanced pro-MMP-9 generation in a cell density-dependent manner under normoxia and OGD. Compatible with observations in a high quality model of focal cerebral ischemia, microglia, but not astrocytes, respond to vitronectin and fibronectin, found when plasma extravasates into the injured region. Astrocytes alone do not generate pro-MMP-9. These events explain the appearance of MMP-9 antigen in association with ischemia-induced cerebral hemorrhage and edema.
- Subjects :
- Pathology
medicine.medical_specialty
Immunocytochemistry
Brain Edema
Matrix metalloproteinase
Brain Ischemia
Brain ischemia
Mice
medicine
Animals
Humans
Zymography
Vitronectin
Cells, Cultured
Enzyme Precursors
biology
Microglia
medicine.disease
Papio anubis
Cell Hypoxia
Fibronectins
Fibronectin
Microglial cell activation
medicine.anatomical_structure
Matrix Metalloproteinase 9
Neurology
Gelatinases
Astrocytes
biology.protein
Original Article
Neurology (clinical)
Cardiology and Cardiovascular Medicine
Intracranial Hemorrhages
Subjects
Details
- ISSN :
- 15597016 and 0271678X
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Journal of Cerebral Blood Flow & Metabolism
- Accession number :
- edsair.doi.dedup.....dcd8c3d793e3fc5457fd28b9e7b32f05