Inosine reduces ischemic brain injury in rats.
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.
Shen
Hui
H
National Institute on Drug Abuse, National Institutes of Health, Baltimore, Md, USA.
Chen
Guann-Juh
GJ
Harvey
Brandon K
BK
Bickford
Paula C
PC
Wang
Yun
Y
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
D007042:Hypoxanthines; D018696:Neuroprotective Agents; D007288:Inosine