Abstract |
Endothelin-1 (ET-1) is up-regulated in the endothelial cells and astrocytes under ischemia. Transgenic mice with astrocytic ET-1 over-expression (GET-1) showed more severe neurological deficit and larger infarct after transient middle cerebral artery occlusion (MCAO). Here, the significance of endothelial ET-1 in ischemic brain injury was investigated using transgenic mice with the endothelial ET-1 over-expression (TET-1). Increased ET-1 level was observed in the TET-1 brain infarct core after transient MCAO. ET(A) receptor expression was induced in the penumbra and ET(A) antagonist (A-147627) partially normalized the infarct volume and neurological deficit. In the infarct core of TET-1 brain, superoxide, nitrotyrosine, and gp91( phox) levels were increased. TET-1 brain displayed increased matrix metalloproteinase-2 expression, water content, immunoglobulin leakage and decreased occludin level in the ipsilateral hemisphere indicative of BBB breakdown and hemispheric edema. Interestingly, AQP-4 expression was increased in the penumbra of TET-1 brain following transient MCAO leading to the water accumulation. Taken together, endothelial ET-1 over-expression and ETA receptor activation contributes to the increased oxidative stress, water accumulation and BBB breakdown after transient MCAO leading to more severe neurological deficit and increased infarct.
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Authors | Justin W C Leung, Stephen S M Chung, Sookja K Chung |
Journal | Brain research
(Brain Res)
Vol. 1266
Pg. 121-9
(Apr 17 2009)
ISSN: 1872-6240 [Electronic] Netherlands |
PMID | 19230825
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aqp4 protein, mouse
- Aquaporin 4
- Endothelin A Receptor Antagonists
- Endothelin-1
- Immunoglobulins
- Membrane Glycoproteins
- Membrane Proteins
- Occludin
- Ocln protein, mouse
- Pyrrolidines
- Receptor, Endothelin A
- Water
- Superoxides
- 3-nitrotyrosine
- Tyrosine
- Cybb protein, mouse
- NADPH Oxidase 2
- NADPH Oxidases
- Receptor, TIE-1
- Matrix Metalloproteinase 2
- Atrasentan
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Topics |
- Animals
- Aquaporin 4
(metabolism)
- Atrasentan
- Blood-Brain Barrier
(pathology, physiopathology)
- Brain
(blood supply, pathology, physiopathology)
- Capillary Permeability
- Endothelin A Receptor Antagonists
- Endothelin-1
(genetics, metabolism)
- Endothelium, Vascular
(pathology, physiopathology)
- Immunoglobulins
(metabolism)
- Infarction, Middle Cerebral Artery
(pathology, physiopathology)
- Matrix Metalloproteinase 2
(metabolism)
- Membrane Glycoproteins
(metabolism)
- Membrane Proteins
(metabolism)
- Mice
- Mice, Transgenic
- NADPH Oxidase 2
- NADPH Oxidases
(metabolism)
- Occludin
- Oxidative Stress
- Promoter Regions, Genetic
- Pyrrolidines
(administration & dosage)
- Receptor, Endothelin A
(metabolism)
- Receptor, TIE-1
(genetics)
- Superoxides
(metabolism)
- Tyrosine
(analogs & derivatives, metabolism)
- Water
(metabolism)
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