New strategies for unclogging microcirculatory obstructions in the healthy and diabetic brain
Recent work from our laboratory has shown that the brain capillaries routinely get 'stuck,' clogged by cells and debris even under healthy conditions. Most of these clogged capillaries clear within seconds to minutes, however, some can remain stuck for much longer. We also reported that about one third of these clogged capillaries were eliminated from the blood vessel network and never get replaced. Importantly, there are certain conditions which can increase the risk of clogged blood vessels in the brain such as diabetes. However, we still do not have a good mechanistic understanding of how these capillary obstructions can be cleared, or even what impact they have on brain function.
In this study, we will characterize capillary obstruction and pruning rates in healthy and diabetic mice brain. Next, we will focus on devising new strategies to enhance the clearance of capillary obstructions. At various time points, the mouse brain will be imaged to assess obstruction clearance and capillary elimination rates. These aims will provide new insights into microcirculatory changes that occur in healthy and diabetic brains, as well as a mechanistic understanding of how capillary obstructions can be cleared.