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

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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