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Microglia potentiate damage to blood-brain barrier constituents: improvement by minocycline in vivo and in vitro.
- Source :
-
Stroke [Stroke] 2006 Apr; Vol. 37 (4), pp. 1087-93. Date of Electronic Publication: 2006 Feb 23. - Publication Year :
- 2006
-
Abstract
- Background: Blood-brain barrier (BBB) disruption after stroke can worsen ischemic injury by increasing edema and causing hemorrhage. We determined the effect of microglia on the BBB and its primary constituents, endothelial cells (ECs) and astrocytes, after ischemia using in vivo and in vitro models.<br />Methods and Results: Primary astrocytes, ECs, or cocultures were prepared with or without added microglia. Primary ECs were more resistant to oxygen-glucose deprivation/reperfusion than astrocytes. ECs plus astrocytes showed intermediate vulnerability. Microglia added to cocultures nearly doubled cell death. This increase was prevented by minocycline and apocynin. In vivo, minocycline reduced infarct volume and neurological deficits and markedly reduced BBB disruption and hemorrhage in mice after experimental stroke.<br />Conclusions: Inhibition of microglial activation may protect the brain after ischemic stroke by improving BBB viability and integrity. Microglial inhibitors may prove to be an important treatment adjunct to fibrinolysis.
- Subjects :
- Acetophenones pharmacology
Animals
Antioxidants pharmacology
Astrocytes pathology
Brain pathology
Brain Ischemia complications
Brain Ischemia metabolism
Brain Ischemia pathology
Cell Death drug effects
Cells, Cultured
Cerebral Hemorrhage etiology
Cerebral Hemorrhage physiopathology
Cerebral Infarction pathology
Coculture Techniques
Endothelial Cells pathology
Glucose deficiency
Hydrogen Peroxide metabolism
Hypoxia metabolism
Male
Mice
Mice, Inbred C57BL
Nervous System Diseases etiology
Nervous System Diseases physiopathology
Superoxides metabolism
Tumor Necrosis Factor-alpha metabolism
Blood-Brain Barrier drug effects
Brain Ischemia physiopathology
Microglia drug effects
Microglia metabolism
Microglia pathology
Minocycline pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4628
- Volume :
- 37
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Stroke
- Publication Type :
- Academic Journal
- Accession number :
- 16497985
- Full Text :
- https://doi.org/10.1161/01.STR.0000206281.77178.ac