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

Journal Article · Thu Feb 01 00:00:00 EST 1990 · Stroke; (USA)

DOI:https://doi.org/10.1161/01.STR.21.2.310· OSTI ID:6993264

Silverstein, F S; McDonald, III, J W; Bommarito, M; Johnston, M V ^[1]

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1. Univ. of Michigan, Ann Arbor (USA)

The phencyclidine analogue ({sup 3}H)(1-(2-thienyl)cyclohexyl)piperidine ({sup 3}H-TCP) binds to the ion channel associated with the N-methyl-D-aspartate receptor channel complex. In vitro autoradiography indicates that the distribution of {sup 3}H-TCP binding in brain closely parallels that of ({sup 3}H)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 {sup 3}H-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 {sup 3}H-TCP binding in hypoxic-ischemic brain was relatively preserved and there were no interhemispheric asymmetries in {sup 3}H-TCP binding densities. In addition, in three unoperated rats decapitated 24 hours after MK-801 treatment, {sup 3}H-TCP binding was reduced by 15-35%; similar bilateral suppression of {sup 3}H-TCP binding was detected in MK-801-treated ligates. Our data indicate that {sup 3}H-TCP autoradiography can be used to assay the efficacy of neuroprotective agents in this experimental model of perinatal stroke.

• OSTI ID: 6993264
• Journal Information: Stroke; (USA), Vol. 21:2; ISSN 0039-2499
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ASPARTIC ACID
RECEPTORS
GLUTAMIC ACID
BIOCHEMICAL REACTION KINETICS
ISCHEMIA
PATHOGENESIS
PIPERIDINES
ANOXIA
AUTORADIOGRAPHY
BRAIN
NEONATES
RATS
TRITIUM COMPOUNDS
AMINES
AMINO ACIDS
ANIMALS
AZINES
BODY
CARBOXYLIC ACIDS
CARDIOVASCULAR DISEASES
CENTRAL NERVOUS SYSTEM
DISEASES
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
KINETICS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRIDINES
REACTION KINETICS
RODENTS
VASCULAR DISEASES
VERTEBRATES
550901* - Pathology- Tracer Techniques