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Inosine reduces ischemic brain injury in rats.

AbstractBACKGROUND AND PURPOSE:
Purinergic nucleoside inosine elicits protection and regeneration during various injuries. The purpose of this study was to examine the protective effects of inosine against cerebral ischemia.
METHODS:
Adult Sprague-Dawley rats were anesthetized. Inosine, hypoxathine, or vehicle was administered intracerebroventricularly before transient right middle cerebral artery occlusion (MCAo). Animals were placed in behavioral chambers 2 days to 2 weeks after MCAo and then euthanized for tri-phenyl-tetrazolium chloride staining. Glutamate release was measured by microdialysis/high-performance liquid chromatography, and single-unit action potentials were recorded from neurons in the parietal cortex.
RESULTS:
Stroke animals receiving inosine pretreatment demonstrated a higher level of locomotor activity and less cerebral infarction. Intracerebroventricular administration of the same dose of hypoxanthine did not confer protection. Coadministration of selective A3 receptor antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191) significantly reduced inosine-mediated protection. Inosine did not alter basal glutamate release, nor did it reduce ischemia-evoked glutamate overflow from cerebral cortex. However, inosine antagonized glutamate-induced electrophysiological excitation in cerebral cortical neurons.
CONCLUSIONS:
Inosine inhibits glutamate postsynaptic responses and reduces cerebral infarction. Its protective effect against ischemia/reperfusion-related insults may involve activation of adenosine A3 receptors.
AuthorsHui Shen, Guann-Juh Chen, Brandon K Harvey, Paula C Bickford, Yun Wang
JournalStroke; a journal of cerebral circulation (Stroke) Vol. 36 Issue 3 Pg. 654-9 (Mar 2005) ISSN: 1524-4628 [Electronic] United States
PMID15692110 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Hypoxanthines
  • Neuroprotective Agents
  • Inosine
Topics
  • Animals
  • Brain Ischemia (etiology, prevention & control)
  • Hypoxanthines (administration & dosage, pharmacology)
  • Infarction, Middle Cerebral Artery (complications, prevention & control)
  • Injections, Intraventricular
  • Inosine (administration & dosage, pharmacology)
  • Male
  • Neuroprotective Agents (administration & dosage, pharmacology)
  • Rats
  • Rats, Sprague-Dawley

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