Pathophysiology and prevention of neuronal damage in major cerebral arterial occlusive disease

重大脑动脉闭塞性疾病神经元损伤的病理生理学和预防

• 批准号: 17590910
• 负责人: YAMAUCHI Hiroshi
• 金额: $ 2.05万
• 依托单位: Kyoto University (2006)Research Institute, Shiga Medical Center (2005)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590910/
• 关键词: large artery disease; selective neuronal damage; benzodiazepine receptor; positron emission tomography; cerebral ischemia; cerebral infarction; benzodiazepine受容体

In patients with atherothrombotic internal carotid artery (ICA) or middle cerebral artery (MCA) occlusive disease, the chronic reduction in cerebral perfusion pressure (chronic hemodynamic compromise) increases the risk for ischemic neuronal damage. However, the relationship between hemodynamic cerebral ischemia and neuronal damage has not been demonstrated in vivo in humans. The clarification of this relationship is important because vascular reconstruction surgery can improve chronic hemodynamic compromise, which might prevent the development of selective neuronal damage as well as infarction. I investigated the pathophysiology of ischemic neuronal damage in atherothrombotic ICA or MCA occlusive disease by imaging of the central type benzodiazepine receptors (BZR), which are expressed by most cortical neurons, with positrom emission tomography and ^<11>C-Flumazenil. At first, in a cross sectional study, we demonstrated that hemodynamic cerebral ischemia due to atherothrombotic major … More cerebral arterial disease cause selective neuronal damage, by showing that 1) selective neuronal damage demonstrated as decreased BZR is associated with borderzone infarction (hemodynamically induced infarction), and 2)increased oxygen extraction fraction (severe hemodynamic impairment). Then, in a longitudinal study, we confirmed the causal relationship between hemodynamic ischemia and selective neuronal damage by showing that a decrease of BZR during follow-up is associated with an increase of oxygen extraction fraction (hemodynamic deterioration). In patients with atherothrombotic ICA or MCA occlusive disease, selective neuronal damage demonstrated as decreased BZR is associated with chronic hemodynamic compromise (misery perfusion). Misery perfusion may be important for the development of selective neuronal damage in atherothrombotic ICA or MCA occlusive disease. Vascular reconstruction surgery in patients with misery perfusion may lead to the prevention of selective neuronal damage. Imaging of BZR may become a tool for quantitatively evaluating the success of future therapeutic interventions for protecting neurons from ischemic damage. Less

在动脉粥样硬化性颈内动脉(ICA)或大脑中动脉(MCA)闭塞症患者中，脑灌流压力的慢性降低(慢性血流动力学损害)增加了缺血性神经元损伤的风险。然而，血流动力学脑缺血与神经元损伤之间的关系在人类体内尚未得到证实。明确这种关系是很重要的，因为血管重建手术可以改善慢性血流动力学损害，这可能防止选择性神经元损伤和脑梗塞的发展。我研究了动脉粥样硬化性血栓性颈内动脉或大脑中动脉闭塞症的缺血性神经元损伤的病理生理学，方法是对大多数皮质神经元表达的中心型苯二氮卓类受体(BZR)进行成像，并进行正电子发射断层扫描和氟马西尼。首先，在一项横断面研究中，我们证明了动脉粥样硬化性血栓形成的主要…导致的血流动力学脑缺血。更多的脑动脉疾病导致选择性神经元损伤，表现为1)选择性神经元损伤，表现为BZR降低与交界区梗塞(血流动力学诱发的梗塞)有关，以及2)氧摄取分数增加(严重的血流动力学损害)。然后，在一项纵向研究中，我们证实了血流动力学缺血和选择性神经元损伤之间的因果关系，表明在随访期间BZR的减少与氧摄取分数的增加(血流动力学恶化)相关。在动脉粥样硬化性血栓性颈内动脉或大脑中动脉闭塞症患者中，选择性神经元损伤表现为BZR降低与慢性血流动力学损害(痛苦灌流)相关。在动脉粥样硬化性血栓形成的ICA或MCA闭塞疾病中，痛苦的灌流可能是导致选择性神经元损伤的重要因素。血管重建手术在痛苦的灌注患者中可能导致选择性神经元损伤的预防。BZR的成像可能成为定量评估未来保护神经元免受缺血性损伤的治疗干预的成功与否的工具。较少

项目成果

Focal glucose hypermetabolism in interictal state of West syndrome

• DOI: 10.1016/j.pediatrneurol.2005.05.019
• 发表时间: 2006-01-01
• 期刊: PEDIATRIC NEUROLOGY
• 影响因子: 3.8
• 作者: Kumada, T;Okazawa, H;Ito, M
• 通讯作者: Ito, M

Selective neuronal damage and borderzone infarction in carotid artery occlusive disease

颈动脉闭塞性疾病中的选择性神经元损伤和边界区梗死

• 发表时间: 2005
• 期刊: J Nucl Med 46・12
• 作者: Nakagoshi A;Fukunaga M;Umeda M;Mori Y;Higuchi T;Tanaka C;Yamauchi H et al.
• 通讯作者: Yamauchi H et al.

Selective neuronal damage and chronic hemodynamic cerebral ischemia

选择性神经元损伤与慢性血流动力学脑缺血

• 发表时间: 2007
• 期刊: Ann Neurol 61・5
• 作者: Okura;Y.;Miyakoshi;A.;Kohyama;K.;Staufenbiel;M.;Matsumoto;Y;Yamauchi H et al.
• 通讯作者: Yamauchi H et al.