Department of Infection, Immunity and Cardiovascular Disease (IICD), University of Sheffield Medical School, Royal Hallamshire Hospital, Sheffield, United Kingdom.
Healthy Lifespan Institute (HELSI), University of Sheffield, Sheffield, United Kingdom.
Elife. 2022 Jan 11;11:e68242. doi: 10.7554/eLife.68242.
Neurovascular coupling is a critical brain mechanism whereby changes to blood flow accompany localised neural activity. The breakdown of neurovascular coupling is linked to the development and progression of several neurological conditions including dementia. In this study, we examined cortical haemodynamics in mouse preparations that modelled Alzheimer's disease (J20-AD) and atherosclerosis (PCSK9-ATH) between 9 and 12 m of age. We report novel findings with atherosclerosis where neurovascular decline is characterised by significantly reduced blood volume, altered levels of oxyhaemoglobin and deoxyhaemoglobin, in addition to global neuroinflammation. In the comorbid mixed model (J20-PCSK9-MIX), we report a 3 x increase in hippocampal amyloid-beta plaques. A key finding was that cortical spreading depression (CSD) due to electrode insertion into the brain was worse in the diseased animals and led to a prolonged period of hypoxia. These findings suggest that systemic atherosclerosis can be detrimental to neurovascular health and that having cardiovascular comorbidities can exacerbate pre-existing Alzheimer's-related amyloid-plaques.
神经血管耦合是一种关键的大脑机制，通过该机制，血液流动会伴随局部神经活动发生变化。神经血管耦合的破坏与包括痴呆症在内的几种神经疾病的发展和进展有关。在这项研究中，我们检查了 9 至 12 个月大的模拟阿尔茨海默病（J20-AD）和动脉粥样硬化（PCSK9-ATH）的小鼠模型中的皮质血液动力学。我们报告了动脉粥样硬化的新发现，其中神经血管下降的特征是血液体积明显减少，氧合血红蛋白和脱氧血红蛋白水平改变，以及全身性神经炎症。在合并的混合模型（J20-PCSK9-MIX）中，我们报告了海马体中淀粉样β斑块增加了 3 倍。一个关键发现是，由于将电极插入大脑而导致的皮质扩散性抑制（CSD）在患病动物中更为严重，导致缺氧时间延长。这些发现表明，系统性动脉粥样硬化可能对神经血管健康有害，并且存在心血管合并症会加剧先前存在的与阿尔茨海默病相关的淀粉样斑块。
