Arterial Stiffness Due to Carotid Calcification Disrupts Cerebral Blood Flow Regulation and Leads to Cognitive Deficits. Issue 9 (7th May 2019)

• Record Type: Journal Article
• Authors: Muhire, Gervais; Iulita, M. Florencia; Vallerand, Diane; Youwakim, Jessica; Gratuze, Maud; Petry, Franck R.; Planel, Emmanuel; Ferland, Guylaine; Girouard, Hélène
• Is Part Of: Journal of the American Heart Association. Volume 8:Issue 9(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-05-07
• Subjects: arterial stiffness -- blood‐brain barrier -- carotid calcification -- cerebral blood flow -- cognitive impairment; Heart -- Diseases -- Periodicals; Cardiovascular system -- Diseases -- Periodicals; Cerebrovascular disease -- Periodicals; Cardiology -- Periodicals; 616.1
• DOI: 10.1161/JAHA.118.011630
• Languages: English
• ISSNs: 2047-9980

Abstract

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.