Understanding kugeln, a new avenue of research in stroke and dementia

Establishing the structure, regulation, and conservation of endothelial “kugeln”

Sheffield researchers are investigating an intriguing phenomenon they discovered in blood vessels in the brain. Understanding how blood vessels develop in the brain may help us to find ways to tackle diseases including stroke and dementia. Looking at the development of the brain’s circulation in zebrafish, this team discovered something surprising. They saw that the cells that form the blood vessels "inflate" and deflate large spheres from their membrane. These spheres contain a molecule called nitric oxide which is essential for blood vessel health. They named these phenomena kugeln (German for sphere) and are now investigating them further. In this project, the team will confirm kugeln are present in the brains of chicks, mice, and humans. They will examine what other cells kugeln contact in the brain, and what is inside them. They will also examine the brains of human patients with a disease called CADASIL, which causes stroke at an early age. They believe that kugeln may play a role in the development of CADASIL, because when they alter the gene that causes CADASIL in zebrafish, kugeln numbers are much reduced. The unexpected discovery of kugeln has opened up an intriguing avenue for the study of diseases that involve the brain’s circulatory system. Understanding kugeln could offer a completely new way to begin to tackle devastating diseases such as CADASIL and other causes of stroke, as well as vascular dementia.