"As we identified this pathway, so many things fell into place," she continues, "We really hope that our work will encourage others to take a closer look at the vascular endothelium in the brain. So far, we think that our findings have far-reaching and really exciting implications for neuroscience, neurology, cardiovascular medicine, radiology, and our overall understanding of how the brain works."
This research was carried out in Hillman's Laboratory for Functional Optical Imaging, led by PhD student and lead author on the study, Brenda Chen. Other lab members who assisted with the study included PhD and MD/PhD students from Columbia Engineering, Neurobiology and Behavior, and Columbia University Medical Center. The group combined their engineering skills with their expertise in neuroscience, biology, and medicine to understand this new aspect of brain physiology.
To tease apart the role of endothelial signaling in the living brain, they had to develop new ways to both image the brain at very high speeds, and also to selectively alter the ability of endothelial cells to propagate signals within intact vessels. The team achieved this through a range of techniques that use light and optics, including imaging using a high-speed camera with synchronized, strobed LED illumination to capture changes in the color, and thus the oxygenation level of flowing blood. Focused laser light was used in combination with a fluorescent dye within the bloodstream to cause oxidative damage to the inner endothelial layer of blood brain arterioles, while leaving the rest of the vessel intact and responsive. The team showed that, after damaging a small section of a vessel using their laser, the vessel no longer dilated beyond the damaged point. When the endothelium of a larger number of vessels was targeted in the same way, the overall blood flow response of the brain to stimulation was significantly decreased.
"Our finding unifies what is known about blood flow regulation in the rest of the body with how it is regulated in the brain," Hillman explains. "This has wider reaching implications since there are many disease states known to affect blood flow regulation in the rest of the body that, until now, were not expected to directly affect brain health." For instance, involvement of the endothelium might explain neural deficits in diabetics; a clue that could lead to new diagnostics tests and treatments for neurological conditions associated with broader cardiovascular problems.