Battini Stéphanie, Cantarutti Nicola, Kotsalos Christos, Roussel Yann, Cattabiani Alessandro, Arnaudon Alexis, Favreau Cyrille, Antonel Stefano, Markram Henry, Keller Daniel
Blue Brain Project, École Polytechnique Fédérale de Lausanne (EPFL), Campus Biotech, 1202 Geneva, Switzerland.
Biomedicines. 2024 Dec 31;13(1):72. doi: 10.3390/biomedicines13010072.
The cerebral microvasculature forms a dense network of interconnected blood vessels where flow is modulated partly by astrocytes. Increased neuronal activity stimulates astrocytes to release vasoactive substances at the endfeet, altering the diameters of connected vessels. Our study simulated the coupling between blood flow variations and vessel diameter changes driven by astrocytic activity in the rat somatosensory cortex. We developed a framework with three key components: coupling between the vasculature and synthesized astrocytic morphologies, a fluid dynamics model to compute flow in each vascular segment, and a stochastic process replicating the effect of astrocytic endfeet on vessel radii. The model was validated against experimental flow values from the literature across cortical depths. We found that local vasodilation from astrocyte activity increased blood flow, especially in capillaries, exhibiting a layer-specific response in deeper cortical layers. Additionally, the highest blood flow variability occurred in capillaries, emphasizing their role in cerebral perfusion regulation. We discovered that astrocytic activity impacted blood flow dynamics in a localized, clustered manner, with most vascular segments influenced by two to three neighboring endfeet. These insights enhance our understanding of neurovascular coupling and guide future research on blood flow-related diseases.
脑微血管形成了一个由相互连接的血管组成的密集网络，其血流部分受星形胶质细胞调节。神经元活动增加会刺激星形胶质细胞在终足释放血管活性物质，改变相连血管的直径。我们的研究模拟了大鼠体感皮层中由星形胶质细胞活动驱动的血流变化与血管直径变化之间的耦合。我们开发了一个包含三个关键组件的框架：血管系统与合成的星形胶质细胞形态之间的耦合、用于计算每个血管段血流的流体动力学模型，以及复制星形胶质细胞终足对血管半径影响的随机过程。该模型根据文献中不同皮层深度的实验血流值进行了验证。我们发现，星形胶质细胞活动引起的局部血管舒张会增加血流量，尤其是在毛细血管中，在较深的皮层层呈现出层特异性反应。此外，毛细血管中血流变异性最高，这突出了它们在脑灌注调节中的作用。我们发现，星形胶质细胞活动以局部、聚集的方式影响血流动力学，大多数血管段受到两到三个相邻终足的影响。这些见解增进了我们对神经血管耦合的理解，并为未来与血流相关疾病的研究提供了指导。
