The effect of cyclohexyladenosine on the periischemic increases of hippocampal glutamate and glycine in the rabbit

Stacey L. Cantor, Mark Zornow, Leonard P. Miller, Tony L. Yaksh

Research output: Contribution to journalArticle

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Abstract

We investigated the ability of N6-cyclohexyladenosine (CHA), a potent and selective agonist of the adenosine A, receptor, to attenuate elevations of levels of extracellular hippocampal glutamate and glycine that result from episodes of transient global cerebral ischemia (TGCI). A total of 30 New Zealand white rabbits were randomly assigned to receive 0 (n = 5), 0.1 (n = 8), 1.0 (n = 6), 10 (n = 6), or 100 (n = 5) μM CHA. The drug was dissolved in artificial CSF (vehicle) and administered via a microdialysis probe placed stereotactically into the dorsal hippocampus. A second microdialysis probe placed into the contralateral hippocampus of each animal was perfused with vehicle alone. Ten minutes of TGCI was induced by neck tourniquet inflation and deliberate hypotension from 0 to 10 min. Microdialysis samples were collected as follows: every 20 min preischemia (at -80, -60, -40, -20, and 0 min); every 5 min during ischemia and in the immediate reperfusion period (at 5, 10, 15, and 20 min); and every 20 min for the remainder of the reperfusion period (at 40, 60, and 80 min). Samples were then analyzed for their concentration of glutamate and glycine by HPLC. Following 10 min of ischemia, glutamate levels increased to a peak of 3.28 ± 0.55 times baseline and returned to preischemic levels by 40 min, i.e., during reperfusion. Glycine concentrations increased to 5.41 ± 0.91 times over baseline and remained elevated for the duration of the study. Glutamate and glycine levels were converted to a release index, which was denned as the fractional increase (relative to levels just before ischemia) in amino acid concentration multiplied by time during ischemia and reperfusion. Regression analysis revealed a significant dose-dependent reduction in the glycine release index (p = 0.03) on the CHA-treated side. The contralateral side showed no such attenuation (p = 0.5). For glutamate, there was a nonsignificant tendency for CHA to reduce dose-dependently glutamate levels (p = 0.054), whereas the contralateral (vehicle-treated) side showed no such tendency (p = 0.2). These results indicate that CHA (0.1-100 μM) has a dose-dependent attenuating effect on the periischemic increase in extracellular glycine levels. Elevated glycine levels may contribute to glutamate's neurotoxicity. It is uncertain to what degree this decrease in glycine levels by CHA may contribute to previously reported cerebral protection.

Original languageEnglish (US)
Pages (from-to)1884-1892
Number of pages9
JournalJournal of Neurochemistry
Volume59
Issue number5
StatePublished - Nov 1992
Externally publishedYes

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Glycine
Glutamic Acid
Rabbits
Reperfusion
Microdialysis
Ischemia
Transient Ischemic Attack
Hippocampus
Purinergic P1 Receptor Agonists
Tourniquets
Economic Inflation
Regression analysis
Adenosine
Hypotension
Animals
Neck
High Pressure Liquid Chromatography
Regression Analysis
Amino Acids
Pharmaceutical Preparations

Keywords

  • Cyclohexyladenosine
  • Global cerebral ischemia
  • Glutamate
  • Glycine
  • Hippocampus
  • Microdialysis

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

The effect of cyclohexyladenosine on the periischemic increases of hippocampal glutamate and glycine in the rabbit. / Cantor, Stacey L.; Zornow, Mark; Miller, Leonard P.; Yaksh, Tony L.

In: Journal of Neurochemistry, Vol. 59, No. 5, 11.1992, p. 1884-1892.

Research output: Contribution to journalArticle

Cantor, Stacey L. ; Zornow, Mark ; Miller, Leonard P. ; Yaksh, Tony L. / The effect of cyclohexyladenosine on the periischemic increases of hippocampal glutamate and glycine in the rabbit. In: Journal of Neurochemistry. 1992 ; Vol. 59, No. 5. pp. 1884-1892.
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