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Titolo:
THE NONCOMPETITIVE AMPA ANTAGONIST LY-300168 (GYKI-53655) ATTENUATES AMPA-INDUCED HIPPOCAMPAL INJURY IN NEONATAL RODENTS
Autore:
LIU XH; WANG P; BARKS JDE;
Indirizzi:
UNIV MICHIGAN,MED CTR,DEPT PEDIAT,8220B,MSRB III,BOX 0646,1150 W MED CTR DR ANN ARBOR MI 48109 UNIV MICHIGAN,MED CTR,DEPT PEDIAT ANN ARBOR MI 48109
Titolo Testata:
Neuroscience letters
fascicolo: 1-2, volume: 235, anno: 1997,
pagine: 93 - 97
SICI:
0304-3940(1997)235:1-2<93:TNAAL(>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
METHYL-D-ASPARTATE; NON-NMDA ANTAGONISTS; BRAIN INJURY; RAT; RECEPTOR; NEUROTOXICITY; DESENSITIZATION; EXCITOTOXICITY; KAINATE; PROTECT;
Keywords:
EXCITOTOXICITY; HIPPOCAMPUS; EXCITATORY AMINO ACID ANTAGONIST; ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONATE; GYKI 53655; NEWBORN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
22
Recensione:
Indirizzi per estratti:
Citazione:
X.H. Liu et al., "THE NONCOMPETITIVE AMPA ANTAGONIST LY-300168 (GYKI-53655) ATTENUATES AMPA-INDUCED HIPPOCAMPAL INJURY IN NEONATAL RODENTS", Neuroscience letters, 235(1-2), 1997, pp. 93-97

Abstract

In contrast with the neuroprotective efficacy of competitive and non-competitive N-methyl-D-aspartate (NMDA) antagonists versus NMDA neurotoxicity, reported neuroprotective effects of non-NMDA antagonists in limiting alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) toxicity have been less robust. We tested the effect of the non-competitive AMPA receptor antagonist LY 300168 (GYKI 53655; E. Lilly) (0.25 or 2.5 mg/kg per dose i.p. x 3 doses vs. vehicle) on AM PA-induced excitotoxic injury in postnatal day 7 (P7) rats. To assess specificity, wetested the effect of LY 300168 (2.5 mg/kg per dose x 3 doses) on NMDA-induced excitotoxic injury. P7 rats received right intrahippocampal injections of either (S)-AMPA (2.5 nmol, n = 67) or NMDA (12.5 nmol, n = 11). Injection of AMPA resulted in right hippocampal atrophy with pyramidal cell loss. LY 300168 treatment produced dose-dependent attenuation of AMPA-induced right hippocampal injury; based on comparisons with left hippocampal volumes, 2.5 nmol AMPA resulted in 42 +/- 3% (mean+/- SEM) right hippocampal volume loss in controls, but only 10 +/- 5% after LY 300168 2.5 mg/kg per dose (P < 0.001; ANOVA). LY 300168 hadno effect on NMDA-induced hippocampal injury. The data support the hypothesis that drugs that allosterically regulate AMPA receptor activity can modulate the response of immature brain to AMPA-mediated injury. (C) 1997 Elsevier Science Ireland Ltd.

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Documento generato il 21/09/20 alle ore 05:24:15