Endothelial calcium dynamics regulating cerebrovascular function and capillary stalling in the healthy and diabetic brain

The brain is a metabolically demanding organ . Mismatch between blood flow and demand (from neurons) leads to a disruption and in extreme cases injury. Because the smallest blood vessels in the brain are narrow, they are prone to becoming obstructed by circulating cells and debris. This is exacerbated in Diabetics, with “sticky” blood vessels. The cells of blood vessels, endothelial cells, are more than just “pipes”, they form large physically connected networks between themselves. An important regulator of these networks, and a signal to communicate between them, is waves of calcium flowing into cells, which can propagate between these cells. How Diabetes affects these networks of blood vessels, and in turn impact the health of the brain is unknown. Thanks to new genetic tools with state of the art microscopes, we can directly observe these calcium fluxes into endothelial cells in the living, awake, mouse brain, and especially when these blood vessels become occluded. Combined with simultaneous monitoring of blood flow and neural activity I will be able to directly measure concurrent changes in brain activity, blood flow and calcium fluxes to investigate these dynamics in the living healthy or Diabetic mammalian brain.