The CNS and cirrhosis:psychobiological approaches

中枢神经系统和肝硬化：心理生物学方法

• 批准号: 6730407
• 负责人: CHARMAINE A STEWART
• 金额: $ 7.78万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6730407
• 关键词: arteriovenous shunt surgery; benzodiazepine receptor; benzodiazepines; blood flow measurement; brain circulation; clinical research; cognition; hepatic coma /encephalopathy; human subject; liver cirrhosis; liver disorder diagnosis; liver transplantation; medical complication; neuropsychological tests; patient oriented research; positron emission tomography; receptor binding; serotonin transporter

DESCRIPTION (provided by applicant): Hepatic encephalopathy (HE) is one of the most common manifestations of decompensated cirrhosis. Approximately 70% of patients with cirrhosis also have subacute hepatic encephalopathy (SHE), as demonstrated on neuropsychological testing. The use of transjugular intrahepatic portosystemic shunts (TIPS), which acts as a side-to-side shunt, has become common to manage complications of cirrhosis. However, TIPS are associated with adverse effects, including worsening of existing HE or the precipitation of overt HE and liver failure. Liver transplantation has become the ideal management for patients who have decompensated liver disease. The principal hypothesis of this proposal is that changes of HE and SHE can be determined by neuropsychological testing and changes in cerebral blood flow (CBF). The Specific Aims are the following: (1) Determine the changes in cognitive function in patients with cirrhosis; (2) Identify changes in CBF and neurotransmitter activity, as assessed by central benzodiazepine receptor binding and serotonin transporter binding after TIPS insertion; (3) Identify changes in CBF and neurotransmitter activity, as assessed by central benzodiazepine receptor binding and serotonin transporter binding after liver transplantation; and (4) Correlate the neuropsychological changes with cognitive function and central benzodiazepine receptor binding and serotonin transporter binding. These Specific Aims will be pursued in 60 subjects: group I will be 20 cirrhotics who will undergo TIPS; group II will be 20 cirrhotic patients who are scheduled to undergo liver transplantation; and group III will be 20 age and sex matched cirrhotic controls. All groups will be studied with a battery of neuropsychological tests and stimulated CBF, using 1502 labeled water, while half of groups I and II will be tested with 11C flumazenil PET or (11C)(+)McN5652 positron emission tomography (PET), in order to determine central benzodiazepine receptor binding and serotonin transporter binding, respectively, before and one month after undergoing TIPS or liver transplantation. The control group will be studied with 11C flumazenil PET or (11C)(+)McN5652 PET at baseline and 1 month, thereafter. In aggregate, these studies will provide a platform to elucidate cognitive and biological mechanisms underlying hepatic encephalopathy with the ultimate goal of enhancing diagnosis and management. Additionally, the proposed studies will be guided by a team of mentors and sponsors and supplemented by a didactic curriculum, all to lay the foundation for eventual independent clinical investigator status.

描述（由申请人提供）： 肝性脑病（HE）是代偿性肝硬化最常见的表现之一。在神经心理学测试中，大约70％的肝硬化患者也患有亚急性肝脑病（SHE）。肝内门体分流器（TIPS）的使用（TIPS）充当左右分流，已成为管理肝硬化并发症的常见。但是，技巧与不良反应有关，包括现有HE或明显的HE和肝脏衰竭的降水。肝移植已成为肝脏疾病代表性代表的患者的理想管理。该提议的主要假设是，HE和她的变化可以通过神经心理学测试和脑血流变化（CBF）确定。具体目的是：（1）确定肝硬化患者认知功能的变化； （2）确定CBF和神经递质活性的变化，如中央苯二氮卓受体结合和尖端插入后的5-羟色胺转运蛋白结合所评估； （3）确定CBF和神经递质活性的变化，如肝移植后中央苯二氮卓受体结合和5-羟色胺转运蛋白结合所评估； （4）将神经心理学的变化与认知功能和中央苯二氮卓受体结合和5-羟色胺转运蛋白结合相关联。这些具体目标将在60个主题中追求：我将是20个cirrhotics，他们将接受提示；第二组将是20例计划接受肝移植的肝硬化患者；第三组将为20岁，性别匹配的肝硬化对照。 All groups will be studied with a battery of neuropsychological tests and stimulated CBF, using 1502 labeled water, while half of groups I and II will be tested with 11C flumazenil PET or (11C)(+)McN5652 positron emission tomography (PET), in order to determine central benzodiazepine receptor binding and serotonin transporter binding, respectively, before and one month after undergoing TIPS or肝移植。对照组将使用11C氟马西尼PET或（11C）（+）MCN5652 PET（在基线和1个月）进行研究。总体而言，这些研究将提供一个平台，以阐明肝脑病的认知和生物学机制，以增强诊断和管理的最终目标。此外，拟议的研究将由导师和赞助商团队的指导，并补充了教学课程，所有这些都为最终独立的临床研究者的状态奠定了基础。