Erythrocytes Are Oxygen-Sensing Regulators of the Cerebral Microcirculation

Summary Energy production in the brain depends almost exclusively on oxidative metabolism. Neurons have small energy reserves and require a continuous supply of oxygen (O 2 ). It is therefore not surprising that one of the hallmarks of normal brain function is the tight coupling between cerebral blood flow and neuronal activity. Since capillaries are embedded in the O 2 -consuming neuropil, we have here examined whether activity-dependent dips in O 2 tension drive capillary hyperemia. In vivo analyses showed that transient dips in tissue O 2 tension elicit capillary hyperemia. Ex vivo experiments revealed that red blood cells (RBCs) themselves act as O 2 sensors that autonomously regulate their own deformability and thereby flow velocity through capillaries in response to physiological decreases in O 2 tension. This observation has broad implications for understanding how local changes in blood flow are coupled to synaptic transmission.