Scientists have discovered a novel behavior of the blood vessels of the brain in zebrafish that may explain some forms of stroke in humans. The previously undescribed large structures are spherical and so have been termed kugeln (German for sphere) by the team. Kugeln persists for an average of 23 min before regressing into the parent vessel.
No cell has ever been shown to develop kugeln in the past, possibly because they are easily mistaken for normal blood vessels. Kugeln contain a molecule called nitric oxide which is essential for the health of blood vessels.
Stroke is a life-threatening condition affecting more than 100,000 people in the UK each year. Some forms of stroke are caused by mutations in genes which the researchers have shown are required to form kugeln. Although the function of kugeln is not yet fully understood, this link to genetic forms of stroke could provide new insights into neurological and cardiovascular research.
The main author of the study, said: "The finding of kugeln highlights the need for basic research to understand the mechanisms of development and disease.
The author added: "We share 70 per cent of our genes with zebrafish. Therefore, zebrafish are hugely important for understanding processes that can lead to human disease."
Kugeln do not communicate with the vessel lumen and can form in the absence of blood flow. They contain little or no cytoplasm, but the majority are highly positive for nitric oxide reactivity. Kugeln do not interact with brain lymphatic endothelial cells (BLECs) and can form in their absence, nor do they perform a scavenging role or interact with macrophages.
Inhibition of actin polymerization, Myosin II, or Notch signalling reduces kugel formation, while inhibition of VEGF or Wnt dysregulation (either inhibition or activation) increases kugel formation. Kugeln represent a novel Notch‐dependent NO‐containing endothelial organelle restricted to the cerebral vessels, of currently unknown function. The ground breaking research has been published in the journal EMBO reports.
The lead author of the study, said: "It is extremely exciting to discover an entirely new process that only happens in brain blood vessels, because this might explain why some mutations cause stroke but not diseases of other arteries.
"If we can discover the function of kugeln we may be able to manipulate them to reduce the effects of stroke."
The next step for researchers is to establish whether kugeln are present in human brains as well as gaining a deeper understanding of the mechanisms and functions of kugeln.
Cerebral blood vessels extrude large transient spherical structures in some forms of stroke!
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