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.
BACKGROUND AND PURPOSE:Purinergicnucleoside 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: Victor Camera Pimentel; Maria Beatriz Moretto; Mariana Colino Oliveira; Daniela Zanini; Ana Maria Sebastião; Maria Rosa Chitolina Schetinger Journal: Mol Cell Biochem Date: 2015-02-27 Impact factor: 3.396
Authors: Filipe Marques Gonçalves; Vivian Binder Neis; Débora Kurrle Rieger; Tanara V Peres; Mark William Lopes; Isabella A Heinrich; Ana Paula Costa; Ana Lúcia S Rodrigues; Manuella P Kaster; Rodrigo Bainy Leal Journal: J Neural Transm (Vienna) Date: 2017-07-10 Impact factor: 3.575
Authors: Filipe Marques Gonçalves; Vivian Binder Neis; Débora Kurrle Rieger; Mark William Lopes; Isabella A Heinrich; Ana Paula Costa; Ana Lúcia S Rodrigues; Manuella P Kaster; Rodrigo Bainy Leal Journal: Purinergic Signal Date: 2016-12-13 Impact factor: 3.765