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• W2061268684 abstract "Although they likely involve activation of N-methyl-D-aspartate (NMDA) receptors, the mechanisms giving rise to perinatal hypoxic-ischemic-induced damages remained unclear. The purpose of the present study was to investigate in vivo the mechanisms regulating the glutamate-induced release of toxic hydroxyl radicals (·OH) in neonatal rat. Anesthetized 7-day-old Wistar rat pups bearing a microdialysis cannula implanted in the striatum were perfused with a solution containing salicylate as an ·OH trap. Hydroxyl radicals formation was evaluated, after a 3 hr postoperative delay, by measuring the 2,3-DHBA levels by HPLC/EC before, during and over 3 hr after the administration of glutamatergic agonists or antagonists. Administration of NMDA and of ibotenate dramatically increased the efflux of ·OH, 17-fold and sixfold, respectively. Glutamate, used at the same concentration did not produce any significant increase in the ·OH release and may even decrease this efflux when given at larger concentrations. The NMDA-induced ·OH response was partially but progressively reduced by glutamate coinjection and completely blunted by DHPG [(RS)-3,5-dihydroxyphenylglycine], a group I metabotropic glutamate receptor agonist. Conversely, AIDA [(RS)-1-aminoindan-1,5-dicarboxylic acid], an antagonist of the same receptors, unmasked an ·OH response to glutamate. These results are evidence that the glutamate-induced activation of a group I metabotropic glutamate receptor normally protected the neonatal brain from any glutamate activation of NMDA receptor, which otherwise would produce the release of toxic hydroxyl radicals. Targeting group I metabotropic glutamate receptors and/or ·OH might contribute to protecting the neonatal brain against perinatal hypoxic-ischemic induced lesions. J. Neurosci. Res. 62:84–90, 2000. © 2000 Wiley-Liss, Inc." @default.
• W2061268684 created "2016-06-24" @default.
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• W2061268684 date "2000-01-01" @default.
• W2061268684 modified "2023-10-11" @default.
• W2061268684 title "N-methyl-D-aspartate but not glutamate induces the release of hydroxyl radicals in the neonatal rat: Modulation by group I metabotropic glutamate receptors" @default.
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• W2061268684 doi "https://doi.org/10.1002/1097-4547(20001001)62:1<84::aid-jnr9>3.0.co;2-u" @default.
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