Maximising a small vessel disease brain bank resource

大脑内部的血液供应来自大血管，这些血管分裂并变小，然后进入脑组织。它们继续分支，变成小动脉，最后变成毛细血管，此时血液中的营养物质进入脑组织。毛细血管然后开始再次结合形成小静脉，将血液从大脑中带走。这些小动脉、毛细血管和小静脉会受到一种称为小血管病（SVD）的疾病过程的影响，这种疾病会损害大脑的深层。这种白色损害可以在脑部扫描，特别是磁共振成像（MRI）上看到，作为一系列不同的病变，包括白色病变（WML），扩大的血管周围空间，微出血和微梗死。这些病变是非常常见的，在几乎一半的痴呆症患者中可见，包括阿尔茨海默病和血管性痴呆。然而，情况很复杂，因为这些变化也可以在其他疾病中看到，包括不同类型的中风，包括脑出血和抑郁症，也可以在没有明显认知问题的衰老中看到。为了充分研究SVD为什么以及如何损害人类大脑，这一过程被称为病理生理学，我们需要在脑损伤的不同阶段观察受SVD影响的人类脑组织。动物模型的用途有限，因为动物不会发生SVD，并且所使用的模型经过遗传修饰，具有人类疾病的某些方面，但不包括全貌。我们的提案将建立一个人脑库，以支持当地、国家和国际上对人类SVD病理生理学的生物医学研究。为了充分做到这一点，我们不仅需要在死后获得脑组织。我们需要获得捐赠大脑的个人的终身医疗记录，以便我们可以评估他们暴露于哪些风险因素（如高血压，糖尿病，肥胖和吸烟史），我们需要将其与生命期间进行的调查联系起来，如脑部扫描（MRI）和血液检查，如胆固醇。由于对患者数据的访问受到非常严格的控制，因此这些数据需要存储在安全的站点（数据安全港）中，并且只能由授权人员访问。研究人员可以提供具有相关临床数据（年龄，性别，BMI，吸烟史，血压等）的组织，但以保密的方式-研究人员无法从所提供的信息中确定捐赠者的身份。到目前为止，我们有几个临床队列在死后捐赠了大脑，我们正在寻找一个类似的大脑捐赠计划，围绕由SVD引起的非常小的中风患者。然后，我们将能够为生物医学研究小组提供人类SVD的所有方面，包括深度小中风，脑出血，有认知问题的SVD和没有认知问题的SVD。

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.