Effects of hypoxia-ischemia and mk-801 treatment on the binding of a phencyclidine analogue in the developing rat brain

Faye S. Silverstein, John W. McDonald, Michael Bommarito, Michael V Johnston

Research output: Contribution to journalArticle

Abstract

The phencyclidine analogue [3H](1-[2-thienyl]cyclohexyl)piperidine (3H-TCP) binds to the ion channel associated with the JV-methyl-D-aspartate receptor channel complex. In vitro autoradiography indicates that the distribution of3H-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 reduced3H-TCP binding ipsilateral to the ligation by 30% in the CA1, by 27% in the CA3, by 26% in the dentate gyms, 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 of3H-TCP binding in hypoxic-ischemic brain was relatively preserved and there were no interhemispheric asymmetries in3H-TCP binding densities. In addition, in three un opera ted rats decapitated 24 hours after MK-801 treatment,3H-TCP binding was reduced by 15-35%; similar bilateral suppression of3H-TCP binding was detected in MK-801-treated ligates. Our data indicate that3H-TCP auto radiography can be used to assay the efficacy of neuroprotective agents in this experimental model of perinatal stroke.

Original languageEnglish (US)
Pages (from-to)310-315
Number of pages6
JournalStroke
Volume21
Issue number2
Publication statusPublished - 1990

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Keywords

  • Anoxia
  • MK-801
  • N-methyl-d-aspartate
  • Rats

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing
  • Neuroscience(all)

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