title: Discrepancy between cell injury and benzodiazepine receptor binding after transient middle cerebral artery occlusion in rats.
abstract: We investigated postischemic alterations in benzodiazepine receptor, D1 dopamine receptor, and muscarinic acetylcholine receptor binding after transient middle cerebral artery (MCA) occlusion in rats using [3H]-flumazenil, [3H]-SCH23390, and [3H]-N-methyl-4-piperidyl benzilate ([3H]-NMPB), respectively, as radioligand. These ligand bindings were determined at 3 and 24 h and at 3 and 7 days after ischemia/reperfusion of MCA by using autoradiographic methods. Ischemic cell injury was clearly detected from 3 h after ischemia/reperfusion and progressively increased from 3-24 h after ischemia/reperfusion of MCA. The area of cell injury reached maximum at 24 h after ischemia/reperfusion of MCA. [3H]-SCH23390 binding was reduced to 47% of the contralateral side at 3 days after ischemia/reperfusion of MCA. After 7 days, [3H]-SCH23390 binding was further reduced by 20% in the striatum. [3H]-NMPB binding was slightly decreased in both the striatum and cerebral cortex at 3 days after ischemia/reperfusion of MCA, and [3H]-NMPB binding in the striatum and cerebral cortex were reduced to 42 and 62% of the contralateral side at 7 days after ischemia/reperfusion of MCA. [3H]-NMPB was also decreased at 24 h. In contrast, [3H]-flumazenil binding was not decreased in the striatum and cerebral cortex within 7 days after ischemia/reperfusion of MCA. These results suggest that [3H]-SCH23390 and [3H]-NMPB binding do not correlate with cell injury by ischemia/reperfusion, although vulnerability to ischemia/reperfusion was observed with these receptors. In addition, central benzodiazepine receptor imaging might be essentially stable to neuronal cell injury induced by transient focal cerebral ischemia in rats, in contrast to the results of PET studies.
authors.affiliation: Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. kohji.abe@shionogi.co.jp
authors.forename: Kohji
authors.initials: K
authors.lastname: Abe
authors.forename: Yuto
authors.initials: Y
authors.lastname: Kashiwagi
authors.forename: Miwa
authors.initials: M
authors.lastname: Tokumura
authors.forename: Rie
authors.initials: R
authors.lastname: Hosoi
authors.forename: Jun
authors.initials: J
authors.lastname: Hatazawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Inoue
mesh_terms: D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000378:metabolism; D001561:Benzilates / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D001667:Binding, Competitive / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D005442:Flumazenil / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010880:Piperidines / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D015427:Reperfusion Injury / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D012680:Sensitivity and Specificity; D014316:Tritium
chemical_list: D001552:Benzazepines; D001561:Benzilates; D010880:Piperidines; D017447:Receptors, Dopamine D1; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D014316:Tritium; D005442:Flumazenil; C020407:enpiperate