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

在动脉粥样硬化性颈内动脉（ICA）或大脑中动脉（MCA）闭塞性疾病患者中，脑灌注压的慢性降低（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尚未在人体体内得到证实。澄清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梗死的发展。我研究了动脉粥样硬化性血栓性ICA或MCA闭塞性疾病中缺血性神经元损伤的病理生理，通过正极发射断层扫描和^<11> c -氟马西尼成像，研究了大多数皮质神经元表达的中枢型苯二氮卓受体（BZR）。首先，在横断面研究中，我们证明了由动脉粥样硬化性血栓性脑缺血引起的血流动力学脑缺血，更多的脑动脉疾病引起选择性神经元损伤，通过显示1)选择性神经元损伤表现为BZR降低与边界区梗死（血流动力学诱导的梗死）有关，2)氧气提取分数增加（严重的血流动力学损伤）。然后，在一项纵向研究中，我们证实了血流动力学缺血与选择性神经元损伤之间的因果关系，表明随访期间BZR的降低与氧气提取分数的增加有关（血流动力学恶化）。在动脉粥样硬化性血栓性ICA或MCA闭塞性疾病患者中，选择性神经元损伤表现为BZR降低，与慢性血流动力学损害（灌注不良）相关。在动脉粥样硬化性血栓性ICA或MCA闭塞性疾病中，悲惨灌注可能对选择性神经元损伤的发展很重要。血管重建手术可以预防选择性神经元损伤。BZR成像可能成为定量评估未来治疗干预是否成功的工具，以保护神经元免受缺血性损伤。少

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