Simulations of blood as a suspension predicts a depth dependent hematocrit in the circulation throughout the cerebral cortex

PLoS Comput Biol. 2018 Nov 19;14(11):e1006549. doi: 10.1371/journal.pcbi.1006549. eCollection 2018 Nov.

Abstract

Recent advances in modeling oxygen supply to cortical brain tissue have begun to elucidate the functional mechanisms of neurovascular coupling. While the principal mechanisms of blood flow regulation after neuronal firing are generally known, mechanistic hemodynamic simulations cannot yet pinpoint the exact spatial and temporal coordination between the network of arteries, arterioles, capillaries and veins for the entire brain. Because of the potential significance of blood flow and oxygen supply simulations for illuminating spatiotemporal regulation inside the cortical microanatomy, there is a need to create mathematical models of the entire cerebral circulation with realistic anatomical detail. Our hypothesis is that an anatomically accurate reconstruction of the cerebrocirculatory architecture will inform about possible regulatory mechanisms of the neurovascular interface. In this article, we introduce large-scale networks of the murine cerebral circulation spanning the Circle of Willis, main cerebral arteries connected to the pial network down to the microcirculation in the capillary bed. Several multiscale models were generated from state-of-the-art neuroimaging data. Using a vascular network construction algorithm, the entire circulation of the middle cerebral artery was synthesized. Blood flow simulations indicate a consistent trend of higher hematocrit in deeper cortical layers, while surface layers with shorter vascular path lengths seem to carry comparatively lower red blood cell (RBC) concentrations. Moreover, the variability of RBC flux decreases with cortical depth. These results support the notion that plasma skimming serves a self-regulating function for maintaining uniform oxygen perfusion to neurons irrespective of their location in the blood supply hierarchy. Our computations also demonstrate the practicality of simulating blood flow for large portions of the mouse brain with existing computer resources. The efficient simulation of blood flow throughout the entire middle cerebral artery (MCA) territory is a promising milestone towards the final aim of predicting blood flow patterns for the entire brain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blood*
  • Cerebral Cortex / blood supply*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / diagnostic imaging
  • Cerebrovascular Circulation*
  • Erythrocyte Count
  • Hematocrit*
  • Hemodynamics / physiology
  • Mice
  • Microcirculation / physiology
  • Models, Biological
  • Neuroglia / cytology
  • Neuroimaging
  • Neurons / cytology
  • Oxygen / metabolism
  • Probability

Substances

  • Oxygen

Grants and funding

The funding sources for this work include AL, National Institute of Health, https://www.nih.gov/ 1R21N099896-01A1 and National Science Foundation CBET-1301198, https://www.nsf.gov/. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of this manuscript.