FIGURE 3.

Capillary flow patterns controlled by pericytes govern the efficacy of oxygen extraction fraction in healthy and ischemic brains. Capillary flow patterns (yellow arrows) govern the efficacy of OEF values. Intravascular colors indicate blood saturation (red, more oxygenated; darker blue, more deoxygenated). In the resting state, RBCs’ velocities vary among capillaries, with little oxygen being extracted from blood. With normal neuronal activity, an increase in blood flow shortens capillary transit times and hence increases CTH-related functional shunting of oxygenated blood. With a more pronounced neuronal activity in a healthy brain, the response of the normal brain to spreading depolarization is accompanied by an increase in blood flow and a short depression in electrical activity. Bottom, pericyte loss and/or neurovascular uncoupling state associated by hyperexcitable neurons in an ischemic brain, an elevated CTTH, and failure of capillary flow patterns to homogenize during hyperemia hinder the redistribution of blood across the capillary bed and a decrease in blood flow in the capillary network, while less affected capillary paths act as functional shunts for oxygenated blood. The accompanying reduction in net oxygen supply reduces tissue oxygen tension as cells continue to use oxygen, increasing blood-tissue concentration gradients and net oxygen extraction. The response of the ischemic brain with dysfunctional pericytes to spreading depolarization is accompanied by a decrease in cerebral blood flow (ischemia) and prolonged depression in electrical activity.