Precapillary sphincters control cerebral blood flow

Active nerve cells produce and release vasodilators that increase their energy supply by dilating local blood vessels, a mechanism termed neurovascular coupling, which is the basis of the BOLD (blood-oxygen-level-dependent) functional neuroimaging signals. We here reveal a unique mechanism for cerebral blood flow control, a precapillary sphincter at the transition between the penetrating arteriole and the first capillary that links blood flow in capillaries to the arteriolar inflow. Large NG2-positive cells, containing smooth muscle actin, encircle the sphincters and rises in nerve cell activity cause astrocyte and neuronal Ca2+ rises that correlate to dilation and shortening of the sphincter concomitant with substantial increases in the RBC flux. Global ischemia and cortical spreading depolarization constrict sphincters and cause vascular trapping of blood cells. These results reveal precapillary sphincters as bottlenecks for brain capillary blood flow.