Depth-dependent flow and pressure characteristics in cortical microvascular networks

Abstract

A better knowledge of the flow and pressure distribution in realistic microvascular networks is needed for improving our understanding of neurovascular coupling mechanisms and the related measurement techniques. Here, numerical simulations with discrete tracking of red blood cells (RBCs) are performed in three realistic microvascular networks from the mouse cerebral cortex. Our analysis is based on trajectories of individual RBCs and focuses on layer-specific flow phenomena until a cortical depth of 1 mm. The individual RBC trajectories reveal that in the capillary bed RBCs preferentially move in plane. Hence, the capillary flow field shows laminar patterns and a layer-specific analysis is valid. We demonstrate that for RBCs entering the capillary bed close to the cortical surface (< 400 μm) the largest pressure drop takes place in the capillaries (37%), while for deeper regions arterioles are responsible for 61% of the total pressure drop. Further flow characteristics, such as capillary transit time or RBC velocity, also vary significantly over cortical depth. Comparison of purely topological characteristics with flow-based ones shows that a combined interpretation of topology and flow is indispensable. Our results provide evidence that it is crucial to consider layer-specific differences for all investigations related to the flow and pressure distribution in the cortical vasculature. These findings support the hypothesis that for an efficient oxygen up-regulation at least two regulation mechanisms must be playing hand in hand, namely cerebral blood flow increase and microvascular flow homogenization. However, the contribution of both regulation mechanisms to oxygen up-regulation likely varies over depth.

Author summary

The brain consumes approximately 20% of the total oxygen used by the human body. An efficient and robust energy supply is essential for the brain’s functioning. The brain is able to up-regulate its oxygen supply in the proximity of neuronal activation. However, the details of the underlying vascular regulation mechanisms remain unknown. To improve the understanding of the blood flow patterns in the cortex we perform numerical simulations in realistic microvascular networks. In contrast to experimental measurements, numerical computations offer the advantage that the whole pressure and flow field is available for analysis. It is well established that the cerebral cortex is organized in laminar fashion and indeed our results reveal that the flow field in the capillary bed shows significant layer-specific differences. Those differences must be taken into account in future numerical and experimental works. Furthermore, it seems likely that multiple regulation mechanisms are playing hand in hand and that their impact differs over depth.