Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, USA.
Center for Neural Engineering, Pennsylvania State University, University Park, PA, USA.
Fluids Barriers CNS. 2022 May 15;19(1):34. doi: 10.1186/s12987-022-00326-y.
The movement of fluid into, through, and out of the brain plays an important role in clearing metabolic waste. However, there is controversy regarding the mechanisms driving fluid movement in the fluid-filled paravascular spaces (PVS), and whether the movement of metabolic waste in the brain extracellular space (ECS) is primarily driven by diffusion or convection. The dilation of penetrating arterioles in the brain in response to increases in neural activity (neurovascular coupling) is an attractive candidate for driving fluid circulation, as it drives deformation of the brain tissue and of the PVS around arteries, resulting in fluid movement. We simulated the effects of vasodilation on fluid movement into and out of the brain ECS using a novel poroelastic model of brain tissue. We found that arteriolar dilations could drive convective flow through the ECS radially outward from the arteriole, and that this flow is sensitive to the dynamics of the dilation. Simulations of sleep-like conditions, with larger vasodilations and increased extracellular volume in the brain showed enhanced movement of fluid from the PVS into the ECS. Our simulations suggest that both sensory-evoked and sleep-related arteriolar dilations can drive convective flow of cerebrospinal fluid not just in the PVS, but also into the ECS through the PVS around arterioles.
脑内液体的流入、通过和流出对于清除代谢废物起着重要作用。然而，关于在充满液体的脑周围腔隙（PVS）中驱动液体流动的机制，以及脑细胞外空间（ECS）中代谢废物的移动主要是由扩散还是对流驱动，仍存在争议。大脑中对神经活动增加的穿透性小动脉扩张（神经血管耦合）是驱动液体循环的一个有吸引力的候选机制，因为它会导致动脉周围脑组织和 PVS 的变形，从而引起液体流动。我们使用脑组织的新型多孔弹性模型模拟了血管扩张对脑 ECS 内液体流入和流出的影响。我们发现，小动脉扩张可以驱动 ECS 内的径向向外的对流流动，并且这种流动对扩张的动力学敏感。模拟睡眠样条件，即更大的血管扩张和脑内细胞外体积增加，显示出 PVS 中的液体更有效地流入 ECS。我们的模拟表明，感觉诱发和与睡眠相关的小动脉扩张不仅可以驱动 PVS 中的脑脊液的对流流动，而且可以通过小动脉周围的 PVS 将脑脊液驱动进入 ECS。
