Arterial Stiffness Due to Carotid Calcification Disrupts Cerebral Blood Flow Regulation and Leads to Cognitive Deficits.

TitleArterial Stiffness Due to Carotid Calcification Disrupts Cerebral Blood Flow Regulation and Leads to Cognitive Deficits.
Publication TypeJournal Article
Year of Publication2019
AuteursMuhire, G, M Iulita, F, Vallerand, D, Youwakim, J, Gratuze, M, Petry, FR, Planel, E, Ferland, G, Girouard, H
JournalJ Am Heart Assoc
Volume8
Issue9
Paginatione011630
Date Published2019 May 07
ISSN2047-9980
Abstract

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-β (Aβ) or tau phosphorylation, although it led to a modest increase in the Aβ40/Aβ42 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.

DOI10.1161/JAHA.118.011630
Alternate JournalJ Am Heart Assoc
PubMed ID31057061
PubMed Central IDPMC6512142