Maximising a small vessel disease brain bank resource

点击翻译按钮获取中文摘要

The blood supply for the interior of the brain comes from large blood vessels which divide and get smaller, and enter the brain tissue. They continue to branch becoming small arterioles and finally capillaries, at which point nutrients from the blood pass in to the brain tissue. The capillaries then begin to join up again to form venules taking blood away from the brain. These arterioles, capillaries and venules can be affected by a disease process called small vessel disease (SVD) which damages the deeper parts of the brain. This white matter damage can be seen on brain scans, particularly magnetic resonance imaging (MRI), as a range of different lesions including white matter lesions (WML), enlarged perivascular spaces, microbleeds and microinfarcts. These lesions are very common, being seen in almost half of all people with dementia, including Alzheimer's disease and vascular dementia. However, the picture is complicated as these changes are also seen in other conditions including different kinds of stroke, including brain haemorrhages, and depression, and are also seen with ageing without obvious cognitive problems.To adequately study why and how SVD damages the human brain, a process known as pathophysiology, we need to look at human brain tissues affected by SVD at different stages of brain injury. Animal models are of limited use, as animals do not get SVD and the models being used are genetically modified to have some aspects of the human disease, but do not encompass the whole picture. Our proposal will develop a human brain bank to support biomedical research into the pathophysiology of human SVD locally, nationally and internationally. To adequately do this we do not just need access to brain tissue after death. We need to have access to the lifelong medical records of individuals donating their brains such that we can assess what risk factors they have been exposed to (such as high blood pressure, diabetes, obesity and smoking history), and we need to link this to investigations that have been undertaken during life, such as brain scans (MRI) and blood tests such as cholesterol. As access to patient data is very tightly controlled, this data needs to be stored in a secured site (a data safe haven) and accessed only by authorised individuals. Researchers can be provided with tissues with associated clinical data (age, sex, BMI, smoking history, blood pressure etc) but in a confidential way- the researcher cannot work out the identity of the donor from the information provided. To date we have several clinical cohorts who have donated brains post mortem, an we are looking to develop a similar brain donation programme around patients who have very small strokes caused by SVD. We will then be able to offer biomedical research groups access to all aspects of human SVD, covering deep small strokes, brain haemorrhages, SVD with cognitive problems, and SVD with no cognitive problems.