期刊
JOURNAL OF THE AMERICAN HEART ASSOCIATION
卷 8, 期 9, 页码 -出版社
WILEY
DOI: 10.1161/JAHA.118.011630
关键词
arterial stiffness; blood-brain barrier; carotid calcification; cerebral blood flow; cognitive impairment
资金
- Heart and Stroke Foundation of Canada
- Fonds de recherche du Quebec-Sante [33237]
- Canadian Foundation for Innovation [20089]
- Natural Sciences and Engineering Research Council of Canada [354722]
- Canadian Institutes of Health Research [MOP-126170, MOP-106423, PCN-102993, MOP-285902]
- Faculty of Medicine, Universite de Montreal
- Groupe de Recherche sur le Systeme Nerveux Central (GRSNC), Universite de Montreal
- Fonds de recherche du Quebec - Sante
- Department of Pharmacology and Physiology of Universite de Montreal
- Faculty of Graduate and Postdoctoral Studies of Universite de Montreal
- Alzheimer Society of Canada
Background-Arterial stiffness is associated with cognitive decline and dementia; however, the precise mechanisms by which it affects the brain remain unclear. Methods and Results-Using a mouse model based on carotid calcification this study characterized mechanisms that could contribute to brain degeneration due to arterial stiffness. At 2 weeks postcalcification, carotid stiffness attenuated resting cerebral blood flow in several brain regions including the perirhinal/entorhinal cortex, hippocampus, and thalamus, determined by autoradiography (P<0.05). Carotid calcification impaired cerebral autoregulation and diminished cerebral blood flow responses to neuronal activity and to acetylcholine, examined by laser Doppler flowmetry (P<0.05, P<0.01). Carotid stiffness significantly affected spatial memory at 3 weeks (P<0.05), but not at 2 weeks, suggesting that cerebrovascular impairments precede cognitive dysfunction. In line with the endothelial deficits, carotid stiffness led to increased blood-brain barrier permeability in the hippocampus (P<0.01). This region also exhibited reductions in vessel number containing collagen IV (P<0.01), as did the somatosensory cortex (P<0.05). No evidence of cerebral microhemorrhages was present. Carotid stiffness did not affect the production of mouse amyloid-beta (A beta) or tau phosphorylation, although it led to a modest increase in the A beta 40/A beta 42 ratio in frontal cortex (P<0.01). Conclusions-These findings suggest that carotid stiffness alters brain microcirculation and increases blood-brain barrier permeability associated with cognitive impairments. Therefore, arterial stiffness should be considered a relevant target to protect the brain and prevent cognitive dysfunctions.
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