Optical coherence tomography of arteriolar diameter and capillary perfusion during spreading depolarizations

Spreading depolarization (SD) is associated with profound oligemia and reduced oxygen availability in the mouse cortex during the depolarization phase. Coincident pial arteriolar constriction has been implicated as the primary mechanism for the oligemia. However, where in the vascular bed the hemodynamic response starts has been unclear. To resolve the origin of the hemodynamic response, we used optical coherence tomography (OCT) to simultaneously monitor changes in the vascular tree from capillary bed to pial arteries in mice during two consecutive SDs 15 minutes apart. We found that capillary flow dropped several seconds before pial arteriolar constriction. Moreover, penetrating arterioles constricted before pial arteries suggesting upstream propagation of constriction. Smaller caliber distal pial arteries constricted stronger than larger caliber proximal arterioles, suggesting that the farther the constriction propagates, the weaker it gets. Altogether, our data indicate that the hemodynamic response to cortical SD originates in the capillary bed.