We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Endothelin-1 overexpression leads to further water accumulation and brain edema after middle cerebral artery occlusion via aquaporin 4 expression in astrocytic end-feet.
- Authors
Lo, Amy C. Y.; Chen, Ann Y. S.; Hung, Victor K. L.; Lai Ping Yaw; Fung, Maggie K. L.; Ho, Maggie C. Y.; Tsang, Margaret C. S.; Chung, Stephen S. M.; Chung, Sookja K.
- Abstract
Stroke patients have increased levels of endothelin-1 (ET-1), a strong vasoconstrictor, in their plasma or cerebrospinal fluid. Previously, we showed high level of ET-1 mRNA expression in astrocytes after hypoxia/ischemia. It is unclear whether the contribution of ET-1 induction in astrocytes is protective or destructive in cerebral ischemia. Here, we generated a transgenic mouse model that overexpress ET-1 in astrocytes (GET-1) using the glial fibrillary acidic protein promoter to examine the role of astrocytic ET-1 in ischemic stroke by challenging these mice with transient middle cerebral artery occlusion (MCAO). Under normal condition, GET-1 mice showed no abnormality in brain morphology, cerebrovasculature, absolute cerebral blood flow, blood–brain barrier (BBB) integrity, and mean arterial blood pressure. Yet, GET-1 mice subjected to transient MCAO showed more severe neurologic deficits and increased infarct, which were partially normalized by administration of ABT-627 (ETA antagonist) 5 mins after MCAO. In addition, GET-1 brains exhibited more Evans blue extravasation and showed decreased endothelial occludin expression after MCAO, correlating with higher brain water content and increased cerebral edema. Aquaporin 4 expression was also more pronounced in astrocytic end-feet on blood vessels in GET-1 ipsilateral brains. Our current data suggest that astrocytic ET-1 has deleterious effects on water homeostasis, cerebral edema and BBB integrity, which contribute to more severe ischemic brain injury.Journal of Cerebral Blood Flow & Metabolism (2005) 25, 998–1011. doi:10.1038/sj.jcbfm.9600108; published online 30 March 2005
- Subjects
CEREBRAL infarction; CEREBROVASCULAR disease; ENDOTHELINS; HYPOXEMIA; ISCHEMIA
- Publication
Journal of Cerebral Blood Flow & Metabolism, 2005, Vol 25, Issue 8, p998
- ISSN
0271-678X
- Publication type
Article
- DOI
10.1038/sj.jcbfm.9600108