Effects of hypoxia-ischemia and MK-801 treatment on the binding of a phencyclidine analogue in the developing rat brain.
The phencyclidine analogue [3H](1-[2-thienyl]cyclohexyl)piperidine (3H-TCP) binds to the ion channel associated with the N-methyl-D-aspartate receptor channel complex. In vitro autoradiography indicates that the distribution of 3H-TCP binding in brain closely parallels that of [3H]glutamate binding to the N-methyl-D-aspartate receptor. In nine 7-day-old rats, an acute focal hypoxic-ischemic insult produced by unilateral carotid artery ligation and subsequent exposure to 8% oxygen acutely reduced 3H-TCP binding ipsilateral to the ligation by 30% in the CA1, by 27% in the CA3, by 26% in the dentate gyrus, and by 17% in the striatum compared with values from the contralateral hemisphere. In 10 littermates that received 1 mg/kg of the neuroprotective noncompetitive N-methyl-D-aspartate antagonist MK-801 immediately before hypoxic exposure, the regional distribution of 3H-TCP binding in hypoxic-ischemic brain was relatively preserved and there were no interhemispheric asymmetries in 3H-TCP binding densities. In addition, in three unoperated rats decapitated 24 hours after MK-801 treatment, 3H-TCP binding was reduced by 15-35%; similar bilateral suppression of 3H-TCP binding was detected in MK-801-treated ligates. Our data indicate that 3H-TCP autoradiography can be used to assay the efficacy of neuroprotective agents in this experimental model of perinatal stroke.
Silverstein
F S
FS
Department of Pediatrics, University of Michigan, Ann Arbor 48104.
McDonald
J W
JW
Bommarito
M
M
Johnston
M V
MV
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D000860:Hypoxia / Q000378:metabolism*; D016202:N-Methylaspartate; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D003986:Dibenzocycloheptenes; D005971:Glutamates; D014316:Tritium; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C012058:tenocyclidine; D010622:Phencyclidine