A new in-silico tool for quantifying the impact of blood flow dynamics on cerebral capillary activity

脑功能与血流自动调节密切相关，血流自动调节小血管直径以满足局部脑代谢需要。最近的实验证据表明，血流对毛细血管壁施加的机械力对启动调节的信号的传递有深远的影响，这种功能预计会在不同的病理条件下受损，如高血压、中风和血管老化。到目前为止，这种现象只能通过离体动物实验来研究，而在离体动物实验中，微血管血流仍然是不确定的。事实上，虽然血管细胞的活性可以通过荧光显微镜测量，但直接测量启动血管调节途径的机械力是不可能的。本项目旨在通过计算模型来表征离体制剂中毛细血管壁和血流之间的机械相互作用。我们将计算在不同实验条件下施加在毛细管网络上的流体机械力，并通过考虑压力依赖的调节机制（这已经在我们以前的工作中建模）。所开发的工具将对实验人员非常有用，因为它将允许在不同的实验设置中重建流体动力学场，并建立表征不同观察到的细胞活动水平的阈值。

The cerebral function is tightly coupled with blood flow autoregulation, which modulates the diameter of small vessels for satisfying the local brain metabolic needs. Recent experimental evidence showed that mechanical forces exerted by blood flow on capillary wall has a profound effect on the transmission of the signal initiating the regulation and this function is expected to be impaired across different pathological conditions such as hypertension, stroke and vascular ageing. So far, this phenomenon can be only studied by means of ex-vivo animal experiments, where the microvascular blood flow remains mostly uncertain. Indeed, although vascular cells activity can be measured through fluorescence microscopy, the direct measurement of the mechanical forces initiating the considered vascular regulatory pathways is not possible.This project aims to characterize the mechanical interaction between capillary wall and blood flow in ex-vivo preparations by using computational modelling. We will compute fluid mechanical forces exerted over capillary networks across different experimental conditions and by accounting for pressure-dependent regulatory mechanisms (which have already been modelled in our previous works).The developed tool will be of great use for experimentalists because it will allow to reconstruct the fluid-dynamic field across different experimental settings and to establish thresholds for characterizing different observed cellular activity levels.