Angiogenic and vasoprotective effects of adrenomedullin on prevention of cognitive decline after chronic cerebral hypoperfusion in mice.
Abstract | BACKGROUND AND PURPOSE: METHODS: RESULTS: After bilateral common carotid artery stenosis, mice overexpressing circulating AM showed significantly faster cerebral perfusion recovery due to substantial growth of the capillaries, the circle of Willis, and the leptomeningeal anastomoses and reduced oxidative damage in vascular endothelial cells compared with wild-type mice. Vascular changes were preceded by upregulation of cAMP, vascular endothelial growth factor, and basic fibroblast growth factor. White matter damage and working memory deficits induced by bilateral common carotid artery stenosis were subsequently restored in mice overexpressing circulating AM. CONCLUSIONS: These data indicate that AM promotes arteriogenesis and angiogenesis, inhibits oxidative stress, preserves white matter integrity, and prevents cognitive decline after chronic cerebral hypoperfusion. Thus, AM may serve as a strategy to tackle subcortical vascular dementia.
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Authors | Takakuni Maki, Masafumi Ihara, Youshi Fujita, Takuo Nambu, Kazutoshi Miyashita, Mahito Yamada, Kazuo Washida, Keiko Nishio, Hidefumi Ito, Hiroshi Harada, Hideki Yokoi, Hiroshi Arai, Hiroshi Itoh, Kazuwa Nakao, Ryosuke Takahashi, Hidekazu Tomimoto |
Journal | Stroke
(Stroke)
Vol. 42
Issue 4
Pg. 1122-8
(Apr 2011)
ISSN: 1524-4628 [Electronic] United States |
PMID | 21393586
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Adrenomedullin
(pharmacology, therapeutic use)
- Animals
- Brain Infarction
(complications, drug therapy, physiopathology)
- Cerebral Arteries
(drug effects, physiology)
- Cognition Disorders
(drug therapy, etiology, physiopathology)
- Disease Models, Animal
- Hypoxia-Ischemia, Brain
(complications, drug therapy, physiopathology)
- Mice
- Neovascularization, Physiologic
(drug effects, physiology)
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