Effects of adenosine agonists and an antagonist on excitatory transmitter release from the ischemic rabbit hippocampus

Julian F. Martinez-Tica, Mark H. Zornow

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The purpose of this study was to determine the effects of adenosine agonists and an antagonist on ischemia-induced extracellular glutamate concentrations in an animal model of transient cerebral ischemia using in vivo cerebral microdialysis. Fifty New Zealand white rabbits were randomly assigned to one of five groups (normothermia, hypothermia, cyclopentyladenosine (CPA), theophylline, or propentofylline). Microdialysis probes were stereotactically placed in the dorsal hippocampus. Twenty minutes before the onset of ischemia, either 1 mg/kg CPA, 5 mg/kg propentofylline, or 20 mg/kg theophylline were administered intravenously. Esophageal temperature was maintained at 38°C, except in the hypothermic animals, which were cooled to 30°C throughout the entire experiment. Two 12-min periods of cerebral ischemia, separated by a 105-min interval of reperfusion, were produced by inflating a neck tourniquet. High-performance liquid chromatography was used to determine the glutamate concentration in the microdialysate. There were no significant increases in glutamate concentrations during the first ischemic period in any of the five groups. During the second ischemic episode, glutamate concentrations in the normothermic group peaked at levels approximately three times higher than the initial values. A similar pattern of changes in glutamate concentrations was observed in the CPA, propentofylline, and theophylline groups. In the hypothermic group, the concentrations of glutamate remained at baseline levels during the entire experiment. Contrary to expectations, neither the adenosine agonists (CPA, propentofylline) nor the antagonist (theophylline) had any effect on extracellular glutamate concentrations in the peri-ischemic period. Although adenosine and its analogs may be cerebroprotective agents, their mechanism of action is not fully understood. The data derived from this study indicates that the acute administration of such agents had no effect on ischemia- induced glutamate release within the hippocampus under these experimental conditions. Based on these results, further work is needed to compare in vivo versus in vitro experimental results in acute and long-term treatment studies with adenosine receptor agonists and antagonists. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)110-115
Number of pages6
JournalBrain Research
Volume872
Issue number1-2
DOIs
StatePublished - Jul 28 2000

Fingerprint

Adenosine
Glutamic Acid
Hippocampus
Rabbits
Theophylline
Ischemia
Microdialysis
Purinergic P1 Receptor Agonists
Purinergic P1 Receptor Antagonists
Tourniquets
Transient Ischemic Attack
Hypothermia
Brain Ischemia
Reperfusion
Neck
Animal Models
High Pressure Liquid Chromatography
Temperature
propentofylline

Keywords

  • Adenosine
  • Cerebral ischemia
  • Glutamate
  • Hippocampus
  • Microdialysis
  • Rabbit

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Effects of adenosine agonists and an antagonist on excitatory transmitter release from the ischemic rabbit hippocampus. / Martinez-Tica, Julian F.; Zornow, Mark H.

In: Brain Research, Vol. 872, No. 1-2, 28.07.2000, p. 110-115.

Research output: Contribution to journalArticle

Martinez-Tica, Julian F. ; Zornow, Mark H. / Effects of adenosine agonists and an antagonist on excitatory transmitter release from the ischemic rabbit hippocampus. In: Brain Research. 2000 ; Vol. 872, No. 1-2. pp. 110-115.
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