The capillary bed offers the largest hemodynamic resistance to the cortical blood supply

Abstract

The cortical angioarchitecture is a key factor in controlling cerebral blood flow and oxygen metabolism. Difficulties in imaging the complex microanatomy of the cortex have so far restricted insight about blood flow distribution in the microcirculation. A new methodology combining advanced microscopy data with large scale hemodynamic simulations enabled us to quantify the effect of the angioarchitecture on the cerebral microcirculation. High-resolution images of the mouse primary somatosensory cortex were input into with a comprehensive computational model of cerebral perfusion and oxygen supply ranging from the pial vessels to individual brain cells. Simulations of blood flow, hematocrit and oxygen tension show that the wide variation of hemodynamic states in the tortuous, randomly organized capillary bed is responsible for relatively uniform cortical tissue perfusion and oxygenation. Computational analysis of microcirculatory blood flow and pressure drops further indicates that the capillary bed, including capillaries adjacent to feeding arterioles (d < 10 mm), are the largest contributors to hydraulic resistance.

The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease

“…Computational studies attempting to assess segmental cerebrovascular resistance have given varying results due to difficulties in setting boundary parameters in idealized networks (Schmid et al, 2017). In two recent studies, in which realistic vascular networks of the mouse somatosensory cortex were used, one attributed the bulk of resistance to arterioles in deep cortical layers and capillaries in superficial layers (Schmid et al, 2017), and the other to capillaries “adjacent to feeding arterioles” (Gould et al, 2017), highlighting the uncertainty of estimating segmental vascular resistance.…”

Hippocampus has lower oxygenation and weaker control of brain blood flow than cortex, due to microvascular differences

“…Capillary pO2 was 15 mmHg (21 M) in V1 and 10 mmHg (14 M) in HC. Oxygen diffusion into the tissue was then simulated (Figure 7d), assuming varying rates of neuronal oxygen consumption corresponding to values reported in rodent tissue 21,22 .…”

“…the rate of ATP synthesis) is maintained at >90% of the maximum throughout the tissue. However, in HC the lower vascular density and lower oxygenation mean that [O2] readily becomes limiting for ATP synthesis for physiological Vmax values (1-3 mM/min 22 ). An inhibition in the rate of oxidative phosphorylation of at least 20% likely occurs in around a tenth of HC volume.…”

Oxygen delivery from the cerebral microvasculature to tissue is governed by a single time constant of approximately 6 seconds

“…Given the importance of the coupling between flow and metabolism, particularly in terms of the neurovascular coupling, there have been a number of models that examine this response. Models that simulate the flow through casts of animal microvascular networks have been developed by a number of authors, for example, Fang et al, Weber et al, Reichold et al, Tsai et al, Guibert et al, Blinder et al, Safaeian et al, Kasischke et al, Linninger et al, Gagnon et al, Gould et al, and Schmid et al . Models based on human data, extracted from postmortem tissue, have also been developed, for example, Lorthois et al …”

“…Such models are, however, required to scale up models of oxygen transport computationally efficiently. They are also important to help to interpret the response to changes in metabolic activity, in particular quantifying the speed of different components of this response; this is difficult as there are many factors acting to balance the supply to and consumption of oxygen in cerebral tissue, although recent models have shown promise in performing these simulations computationally efficiently, see for example, Gould et al . The classical view that it is hypoxia that drives changes in flow has now been largely superseded by the idea that it is a parallel process with two separate responses, Buxton .…”