Perivascular pumping of cerebrospinal fluid in the brain with a valve mechanism.
Perivascular pumping of cerebrospinal fluid in the brain with a valve mechanism.
复制标题
通过瓣膜机制在大脑中血管周围泵送脑脊液。
DOI：
10.1098/rsif.2023.0288
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Kelley,DouglasH
中科院分区：
文献类型：
--
作者：
Gan,Yiming;Holstein-Rønsbo,Stephanie;Nedergaard,Maiken;Boster,KimberlyAS;Thomas,JohnH;Kelley,DouglasH
脑脊髓液（CSF）沿着血管周围间隙（PVS）的流动是大脑清除代谢废物系统的重要组成部分。实验表明，心脏搏动和功能性充血引起的动脉运动可使脑脊液沿与血流相同的方向流动，但产生这种方向性的机制尚不清楚。星形胶质细胞终足与穿通动脉的PVS结合，将其与脑细胞外间隙（ECS）分离，并可能调节两个室之间的流动。在这里，我们提出了两个模型，一个是基于流体动力学的完整方程，另一个是使用集总参数，其中星形胶质细胞端足作为阀门，调节PVS和ECS之间的流量。在这两种模型中，心脏脉动驱动净CSF流量与先前的实验观察结果一致。功能性充血，与心脏搏动一起作用，增加净流量。我们还发现，在协议与实验，减少净流量在清醒期间，由于已知的减少ECS渗透性相比，睡眠状态。我们提出了穿通动脉在小鼠体内成像，我们用它来准确地测量他们的收缩和扩张的幅度在心脏搏动和功能性充血，模型的重要输入。我们的模型可用于探索其他输入参数变化的影响，例如由衰老或疾病引起的变化，因为这些参数的更好测量变得可用。
The flow of cerebrospinal fluid (CSF) along perivascular spaces (PVSs) is an important part of the brain’s system for clearing metabolic waste. Experiments reveal that arterial motions from cardiac pulsations and functional hyperaemiadrive CSF in the same direction as the blood flow, but the mechanism producing this directionality is unclear. Astrocyte endfeet bound the PVSs of penetrating arteries, separating them from brain extracellular space (ECS) and potentially regulating flow between the two compartments. Here, we present two models, one based on the full equations of fluid dynamics and the other using lumped parameters, in which the astrocyte endfeet function as valves, regulating flow between the PVS and the ECS. In both models, cardiac pulsations drive a net CSF flow consistent with prior experimental observations. Functional hyperaemia, acting with cardiac pulsation, increases the net flow. We also find, in agreement with experiments, a reduced net flow during wakefulness, due to the known decrease in ECS permeability compared to the sleep state. We presentin vivoimaging of penetrating arteries in mice, which we use to measure accurately the amplitude of their constrictions and dilations during both cardiac pulsation and functional hyperaemia, an important input for the models. Our models can be used to explore the effects of changes in other input parameters, such as those caused by ageing or disease, as better measurements of these parameters become available.