156 Capillary-Level Control of Cerebrovascular Tone

Abstract INTRODUCTION: Activity-induced blood flow increases make up the basis for functional brain imaging and are central to normal brain function. Conventionally, cerebral blood flow is thought to be controlled by arterioles that alter brain intraparenchymal vascular tone to subsequently increase or decrease blood flow through downstream capillaries. We present data that challenge the concept that capillaries are merely passive players in blood flow regulation, and propose that not only do capillaries participate in functional hyperemia, they also help maintain brain vascular resistance. METHODS: In vivo 2-photon microscopy was used to evaluate hind limb stimulation-evoked hyperemia in capillaries, arterioles, and venules of the murine somatosensory cortex. In some in vivo imaging experiments, hypercapnia was induced by adding 5% carbon dioxide to the inspired air. RESULTS: We report that sensory stimulation-evoked hyperemia in the murine cerebral cortex is initiated in capillary beds, rather than in pial or penetrating cortical arterioles. Using 2-photon imaging, we found that red blood cell (RBC) flow velocities increased in capillaries before cortical arterioles during functional hyperemia. Furthermore, mild hypercapnia resulted in baseline cortical arterial vasodilation but failed to alter basal capillary blood flow or suppress capillary hyperemic responses to sensory stimulation. CONCLUSION: These findings support the hypothesis that brain capillaries can regulate local blood flow during neuronal activity. In addition, the preservation of capillary RBC flow velocities and hyperemic responsiveness during mild hypercapnia indicates that capillaries possess intrinsic vascular tone and that arterial vasodilation neither drives nor is required for functional hyperemia. Capillaries are not only able to actively participate in functional hyperemia, but may also serve as a site of vascular autoregulation in the brain, potentially providing an additional layer of protection against extremes in cerebral blood supply produced by physiological systemic blood flow fluctuations.