Abstract
Our understanding of how capillary blood flow and oxygen distribute across cortical layers to meet the local metabolic demand is incomplete. We addressed this question by using two-photon imaging of resting-state microvascular oxygen partial pressure (PO2) and flow in the whisker barrel cortex in awake mice. Our measurements in layers I-V show that the capillary red-blood-cell flux and oxygenation heterogeneity, and the intracapillary resistance to oxygen delivery, all decrease with depth, reaching a minimum around layer IV, while the depth-dependent oxygen extraction fraction is increased in layer IV, where oxygen demand is presumably the highest. Our findings suggest that more homogeneous distribution of the physiological observables relevant to oxygen transport to tissue is an important part of the microvascular network adaptation to local brain metabolism. These results will inform the biophysical models of layer-specific cerebral oxygen delivery and consumption and improve our understanding of the diseases that affect cerebral microcirculation.
Highlights
Normal brain functioning is critically dependent on the adequate and uninterrupted supply of oxygen to brain tissue (Attwell and Laughlin, 2001; Raichle and Gusnard, 2002; Raichle et al, 2001)
We report that 1) in the whisker barrel cortex in awake mice the oxygen extraction fraction (OEF), measured at different cortical depths, reaches its maximum at the depth range of 320–450 mm, corresponding to cortical layer IV, where the neuron and capillary densities are the largest, and, presumably, oxygen consumption is the highest; and 2) the increased OEF is accompanied by the more homogenously distributed capillary PO2 and RBC flux, as well as by a decrease in the intracapillary resistance to oxygen delivery
Oxygen extraction fraction increases in the deeper cortical layers
Summary
Normal brain functioning is critically dependent on the adequate and uninterrupted supply of oxygen to brain tissue (Attwell and Laughlin, 2001; Raichle and Gusnard, 2002; Raichle et al, 2001). Neuronal and microvascular densities vary greatly between cortical layers (Blinder et al, 2013; Sakadzicet al., 2014; Weber et al, 2008; Wu et al, 2016), suggesting a laminar variation of tissue metabolism (de Kock et al, 2007; Hyder et al, 2013) It is still not well understood how blood flow and oxygenation are distributed through the microvascular network to support an adequate tissue oxygenation across the closely spaced, but morphologically and metabolically heterogeneous cortical layers. Answering this question is important to improve our understanding of the normal brain physiology as well as brain diseases that affect cerebral microcirculation (Berthiaume et al, 2018; Iadecola, 2016; Iadecola, 2017; Pantoni, 2010; Zlokovic, 2011)
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