title: Inosine reduces ischemic brain injury in rats.
abstract: OBJECTIVE
  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.
authors.affiliation: National Institute on Drug Abuse, National Institutes of Health, Baltimore, Md, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Guann-Juh
authors.initials: GJ
authors.lastname: Chen
authors.forename: Brandon K
authors.initials: BK
authors.lastname: Harvey
authors.forename: Paula C
authors.initials: PC
authors.lastname: Bickford
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control*; D007042:Hypoxanthines / Q000008:administration & dosage / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000517:prevention & control; D007276:Injections, Intraventricular; D007288:Inosine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007042:Hypoxanthines; D018696:Neuroprotective Agents; D007288:Inosine