From the Sunnybrook Research Institute, Toronto, Canada (P.B., T.L.B., M.M.K., M.E.H., A.L., A.T., L.T., A.D., C.L.L., I.L.J., J.M., B.S.).
CReATe Research Program, Toronto, Canada (D.G., C.L.L.).
Hypertension. 2019 Oct;74(4):1041-1051. doi: 10.1161/HYPERTENSIONAHA.119.13187. Epub 2019 Sep 3.
Transient hypertension is a risk factor for Alzheimer disease (AD), but the effects of this interaction on brain vasculature are understudied. Addressing vascular pathology is a promising avenue to potentiate the efficacy of treatments for AD. We used arterial spin labeling magnetic resonance imaging to longitudinally assess brain vascular function and immunohistopathology to examine cerebrovascular remodeling and amyloid load. Hypertension was induced for 1 month by administration of l-N-nitroarginine-methyl-ester in TgF344-AD rats at the prodromal stage. Following hypertension, nontransgenic rats showed transient cerebrovascular changes, whereas TgF344-AD animals exhibited sustained alterations in cerebrovascular function. Human umbilical cord perivascular cells in combination with scyllo-inositol, an inhibitor of Aβ oligomerization, resulted in normalization of hippocampal vascular function and remodeling, in contrast to either treatment alone. Prodromal stage hypertension exacerbates latter AD pathology, and the combination of human umbilical cord perivascular cells with amyloid clearance promotes cerebrovascular functional recovery.
短暂性高血压是阿尔茨海默病（AD）的一个风险因素，但这种相互作用对大脑血管的影响还研究得不够。解决血管病理学是增强 AD 治疗效果的一个有前途的途径。我们使用动脉自旋标记磁共振成像（ASL-MRI）来纵向评估脑血管功能，并通过免疫组织病理学检查来观察脑血管重塑和淀粉样蛋白负荷。在 AD 模型 TgF344 大鼠的前驱期，通过给予 L-N-硝基精氨酸甲酯诱导高血压 1 个月。高血压后，非转基因大鼠表现出短暂的脑血管变化，而 TgF344-AD 动物则表现出持续的脑血管功能改变。人脐带来源的血管周细胞与 scyllo-肌醇（一种 Aβ 寡聚体抑制剂）联合使用，可使海马血管功能和重塑正常化，而单独使用任何一种药物都没有这种效果。前驱期高血压会加重 AD 后期的病理变化，而人脐带来源的血管周细胞与淀粉样蛋白清除的联合应用可促进脑血管功能的恢复。
