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

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Guylaine Ferland¹  Diane Vallerand²  Gervais Muhire²  Hélène Girouard²  Jessica Youwakim²  Maud Gratuze³  Franck R. Petry³  Emmanuel Planel³  M. Florencia Iulita⁴ 

[1] Département de Nutrition Université de Montréal Québec Canada;Département de Pharmacologie et Physiologie Université de Montréal Québec Canada;Département de Psychiatrie et Neurosciences Université Laval Québec Québec Canada;Groupe de Recherche sur le Système Nerveux Central Université de Montréal Québec Canada;

关键词: arterial stiffness;    blood‐brain barrier;    carotid calcification;    cerebral blood flow;    cognitive impairment;   

DOI  :  10.1161/JAHA.118.011630

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown