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: Kohji Abe, Yuto Kashiwagi, Miwa Tokumura, Rie Hosoi, Jun Hatazawa, Osamu Inoue
• Journal: Synapse (New York, N.Y.) (Synapse) Vol. 53 Issue 4 Pg. 234-9 (Sep 15 2004) ISSN: 0887-4476 [Print] United States
• PMID: 15266555 (Publication Type: Journal Article)

Chemical References

• Benzazepines
• Benzilates
• Piperidines
• Receptors, Dopamine D1
• Receptors, GABA-A
• Receptors, Muscarinic
• Tritium
• Flumazenil
• enpiperate

Topics

• Animals
• Autoradiography
• Benzazepines (metabolism)
• Benzilates (metabolism)
• Binding Sites (physiology)
• Binding, Competitive (physiology)
• Cerebral Cortex (metabolism, pathology, physiopathology)
• Cerebral Infarction (metabolism, pathology, physiopathology)
• Corpus Striatum (metabolism, pathology, physiopathology)
• Disease Models, Animal
• Down-Regulation (physiology)
• Flumazenil (metabolism)
• Infarction, Middle Cerebral Artery (metabolism, pathology, physiopathology)
• Male
• Nerve Degeneration (metabolism, pathology, physiopathology)
• Piperidines (metabolism)
• Radioligand Assay
• Rats
• Rats, Wistar
• Reaction Time (physiology)
• Receptors, Dopamine D1 (metabolism)
• Receptors, GABA-A (metabolism)
• Receptors, Muscarinic (metabolism)
• Reperfusion Injury (diagnosis, metabolism, pathology)
• Sensitivity and Specificity
• Tritium