Why is this research needed?
Stroke, as well as a condition named small vessel disease (SVD), are the major risk factors for vascular dementia with devastating effects in the brain. In SVD, people have damage to blood vessels in the brain which disrupts the vital supply of blood.
Blood vessels also have an important function in removing waste from the brain. Professor Roxanna Carare’s team have previously shown that the elimination of waste from the brain is along tiny channels embedded in the walls of blood vessels. In SVD, this could be disrupted.
However, research that can lead to treatments for SVD remains at an early stage. This is partly because animal models for SVD are not developed to mimic human SVD. Research in animals is needed before treatments can be tested in humans.
What is the aim of this project?
In this project, Roxanna’s team has identified animal models that could be parallel to the human brain to understand why SVD causes damage to the brain. They have specifically looked at animal models that could understand how problems with the removal of waste in the brain contribute to the disease.
What will happen during the project?
Roxanna’s team used two types of mice that are bred specifically for research into these conditions. They have:
- Used a sophisticated method called electron microscopy, a technique allowing researchers to magnify 50,000 times and therefore see tiny features in blood vessels. This helped to understand which type of mice can best be used to understand SVD and vascular dementia in the human brain.
- Injected the mice with fluid similar to the waste products of the human brain that allows researchers to see what could be going wrong in the brain that impedes the removal of waste and could lead to SVD and vascular dementia.
What difference could this research make?
This research into mice models of SVD will improve researchers’ abilities to understand problems with waste removal in the brain that may underlie brain damage. Researchers can then work to develop treatments to address SVD, as well treatments to prevent stroke and vascular dementia that can be caused by SVD.
Roxanna’s team successfully used electron micrographs to identify mice that would be the most appropriate model for SVD. They ruled out the use of one type of mouse bred to mimic these conditions in the brain as it didn’t show features of problems with waste removal in the brain.
They bred a new type of mouse that showed problems in the brain. The model where a type of protein that is normally found in blood vessels, called alpha-dystrobrevin, is missing showed leakage of blood into the brain and abnormal pathways for elimination of waste. Their behaviour was also abnormal. Future research will look at if problems seen in the brains of these mice are similar to those seen in humans with SVD and vascular dementia.
By identifying this new model for SVD in the brain to understand why damage is caused, researchers can now look to test new strategies for therapies to combat the causes of SVD, stroke and vascular dementia.
Roxanna said: “The Stroke Association is a leading charity in the study of vascular dementia due to its connection with stroke. Through the generosity of the Stroke Association in funding this project, we are a step closer to understanding a key mechanism underlying vascular dementia and therefore the design of appropriate therapeutic strategies.”
The results of this research were published in Acta Neuropathologica Communications in August 2020.