Inosine reduces ischemic brain injury in rats

Stroke. 2005 Mar;36(3):654-9. doi: 10.1161/01.STR.0000155747.15679.04. Epub 2005 Feb 3.


Background 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Ischemia / etiology
  • Brain Ischemia / prevention & control*
  • Hypoxanthines / administration & dosage
  • Hypoxanthines / pharmacology
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / prevention & control
  • Injections, Intraventricular
  • Inosine / administration & dosage
  • Inosine / pharmacology*
  • Male
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology
  • Rats
  • Rats, Sprague-Dawley


  • Hypoxanthines
  • Neuroprotective Agents
  • Inosine