title: Silent cortical neuronal damage in atherosclerotic disease of the major cerebral arteries.
abstract: In atherosclerotic internal carotid artery (ICA) or middle cerebral artery (MCA) disease, hemodynamic compromise may cause selective neuronal damage manifested as loss of central benzodiazepine receptors (BZRs) in the normal-appearing cerebral cortex, without overt episode of stroke. To investigate the association of decreases in cortical BZRs with hemodynamic compromise and the effect of angiotensin receptor blockers (ARBs) on these receptors in patients whose atherosclerotic ICA or MCA disease is asymptomatic, we measured BZRs using positron emission tomography and (11)C-flumazenil in 79 patients with asymptomatic atherosclerotic ICA or MCA disease and no cortical infarction. Three-dimensional stereotactic surface projections were used to calculate the BZR index, a measure of abnormally decreased BZRs in the cerebral cortex within the MCA distribution. Multiple regression analysis showed this index to be positively correlated with the value of oxygen extraction fraction, with the presence of silent subcortical infarcts, and with the presence of ischemic heart disease, whereas it was negatively correlated with the treatment of hypertension with ARBs. In asymptomatic atherosclerotic ICA or MCA disease, hemodynamic compromise is associated with selective neuronal damage manifested as decreases in cortical BZRs in the noninfarcted cerebral cortex, whereas ARBs are associated with preservation of cortical BZRs.
authors.affiliation: Department of Functional Neuroimaging, Human Brain Research Center, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan. yamauchi@kuhp.kyoto-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamauchi
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishii
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Higashi
authors.forename: Shinya
authors.initials: S
authors.lastname: Kagawa
authors.forename: Hidenao
authors.initials: H
authors.lastname: Fukuyama
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D050197:Atherosclerosis / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D002343:Carotid Artery, Internal; D002539:Cerebral Arterial Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005442:Flumazenil; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D012044:Regression Analysis
chemical_list: D057911:Angiotensin Receptor Antagonists; D011963:Receptors, GABA-A; D005442:Flumazenil