Maximising a small vessel disease brain bank resource

最大化小血管疾病脑库资源

• 批准号: MR/R014140/1
• 负责人: Colin Smith
• 金额: $ 57.54万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR014140%2F1
• 关键词: Maximising; small; vessel; disease; brain

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.

大脑内部的血液供应来自大血管，大血管分裂变小，进入脑组织。它们继续分支成为小动脉，最后成为毛细血管，此时血液中的营养物质进入脑组织。然后毛细血管开始再次连接形成静脉，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叫做小血管疾病（SVD）的疾病的影响，这种疾病会损害大脑的深层部分。这种白质损伤可以在脑部扫描，特别是磁共振成像（MRI）上看到，表现为一系列不同的病变，包括白质病变（WML）、血管周围空间扩大、微出血和微梗死。这些病变非常常见，在几乎一半的痴呆症患者（包括阿尔茨海默病和血管性痴呆）身上都能看到。然而，情况很复杂，因为这些变化也可以在其他情况下看到，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损伤人脑的原因和方式，这一过程被称为病理生理学，我们需要观察在脑损伤的不同阶段受SVD影响的人脑组织。动物模型的用途有限，因为动物不会得到SVD，而且所使用的模型是经过基因改造的，具有人类疾病的某些方面，但不能涵盖全部情况。我们的建议是建立一个人类脑库，以支持当地、国内和国际上对人类SVD病理生理学的生物医学研究。为了充分做到这一点，我们不仅需要在人死后获取脑组织。我们需要获得捐献大脑的个人的终身医疗记录，这样我们就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），我们需要将其与一生中进行的调查联系起来，如脑部扫描（MRI）和血液测试（如胆固醇）。由于对患者数据的访问受到严格控制，这些数据需要存储在一个安全的地点（数据安全港），只有获得授权的个人才能访问。研究人员可以获得带有相关临床数据（年龄、性别、身体质量指数、吸烟史、血压等）的组织，但必须保密——研究人员无法从提供的信息中确定捐赠者的身份。到目前为止，我们已经有几个临床队列在死后捐赠了大脑，我们正在寻求针对由SVD引起的非常小的中风的患者开发类似的大脑捐赠计划。届时，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。

项目成果

Small vessels, dementia and chronic diseases - molecular mechanisms and pathophysiology.

• DOI: 10.1042/cs20171620
• 发表时间: 2018-04-30
• 期刊: Clinical science (London, England : 1979)
• 作者: Horsburgh K;Wardlaw JM;van Agtmael T;Allan SM;Ashford MLJ;Bath PM;Brown R;Berwick J;Cader MZ;Carare RO;Davis JB;Duncombe J;Farr TD;Fowler JH;Goense J;Granata A;Hall CN;Hainsworth AH;Harvey A;Hawkes CA;Joutel A;Kalaria RN;Kehoe PG;Lawrence CB;Lockhart A;Love S;Macleod MR;Macrae IM;Markus HS;McCabe C;McColl BW;Meakin PJ;Miller A;Nedergaard M;O'Sullivan M;Quinn TJ;Rajani R;Saksida LM;Smith C;Smith KJ;Touyz RM;Trueman RC;Wang T;Williams A;Williams SCR;Work LM
• 通讯作者: Work LM

Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem human brains.

• DOI: 10.1136/jnnp-2017-317234
• 发表时间: 2018-08
• 期刊: Journal of neurology, neurosurgery, and psychiatry
• 作者: Keogh MJ;Wei W;Aryaman J;Wilson I;Talbot K;Turner MR;McKenzie CA;Troakes C;Attems J;Smith C;Al Sarraj S;Morris CM;Ansorge O;Pickering-Brown S;Jones N;Ironside JW;Chinnery PF
• 通讯作者: Chinnery PF

Brain donation procedures in the Sudden Death Brain Bank in Edinburgh.

爱丁堡猝死脑库的大脑捐赠程序。

• DOI: 10.1016/b978-0-444-63639-3.00002-5
• 发表时间: 2018
• 期刊: Handbook of clinical neurology
• 作者: Smith C

A protocol for precise comparisons of small vessel disease lesions between ex vivo magnetic resonance imaging and histopathology.

• DOI: 10.1177/1747493018799962
• 发表时间: 2019-04
• 期刊: International journal of stroke : official journal of the International Stroke Society
• 作者: Humphreys CA;Jansen MA;Muñoz Maniega S;González-Castro V;Pernet C;Deary IJ;Al-Shahi Salman R;Wardlaw JM;Smith C
• 通讯作者: Smith C

The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: model development and diagnostic test accuracy study.

• DOI: 10.1016/s1474-4422(18)30006-1
• 发表时间: 2018-03
• 期刊: The Lancet. Neurology
• 作者: Rodrigues MA;Samarasekera N;Lerpiniere C;Humphreys C;McCarron MO;White PM;Nicoll JAR;Sudlow CLM;Cordonnier C;Wardlaw JM;Smith C;Al-Shahi Salman R
• 通讯作者: Al-Shahi Salman R