Microvascular network organization and hemodynamic perfusion protect the brain against hypoxia.

Abstract

Mechanistic simulations of blood flow and oxygen exchange showed regions of cortical tissue tolerating substantial increase in local oxygen consumption (CMRO₂) before reaching hypoxia (pO₂ < 10 mmHg). The observed robustness in O₂ supply was attributed to overcapacity in convective oxygen transport in the pial arterial network combined with a surplus in the number of capillary flow paths. Microcirculatory flux analysis suggests that <i>network</i> induced hemodynamic flow patterns impart <i>intrinsic reserve</i> to protect the brain against perfusion variances or metabolic demand surges during activation. Furthermore, oxygen transport in cortical tissue is characterized by two regimes: in the <i>transport zone-</i>centered on <i>penetrating arteriole trees</i> composed of a single penetrating vessel connected to the post-arteriole capillary transition zone-strong diffusion supports high oxygen tension with only modest contribution from capillaries. This regime transitions into the <i>terminal/reactive zone</i> where oxygenation is sensitive to capillary density and perfusion. Quasi-dynamic simulations also enabled reconstruction of the BOLD signal underlying functional imaging. Simulations at single micron resolution further show that age-related reductions in arterial saturation and systemic hematocrit were sufficient to induce hypoxic tissue pockets in the terminal zone at nominal perfusion (CBF) and metabolic activity (CMRO₂), and neutrophil adhesion induced capillary flow stalling further exacerbates hypoxia.