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Titolo:
The neuroprotective and hypothermic effect of GYKI-52466, a non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-antagonist on histological and behavioural variables in the gerbil global ischemia model
Autore:
Gyertyan, I; Gigler, G; Simo, A;
Indirizzi:
EGIS Pharmaceut Ltd, Dept CNS Pharmacol, H-1475 Budapest, Hungary EGIS Pharmaceut Ltd Budapest Hungary H-1475 ol, H-1475 Budapest, Hungary
Titolo Testata:
BRAIN RESEARCH BULLETIN
fascicolo: 3, volume: 50, anno: 1999,
pagine: 179 - 186
SICI:
0361-9230(199910)50:3<179:TNAHEO>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSIENT CEREBRAL-ISCHEMIA; NEURONAL DAMAGE; FOREBRAIN ISCHEMIA; LOCOMOTOR-ACTIVITY; MONGOLIAN GERBILS; BRAIN TEMPERATURE; HIPPOCAMPUS; DEGENERATION; MAZE; AMPA;
Keywords:
cerebral ischemia; GYKI-52466; neuroprotection; hypothermia; spontaneous alternation; hippocampal neuronal damage;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Gigler, G EGIS Pharmaceut Ltd, Dept CNS Pharmacol, POB 100, H-1475 Budapest, Hungary EGIS Pharmaceut Ltd POB 100 Budapest Hungary H-1475 st, Hungary
Citazione:
I. Gyertyan et al., "The neuroprotective and hypothermic effect of GYKI-52466, a non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-antagonist on histological and behavioural variables in the gerbil global ischemia model", BRAIN RES B, 50(3), 1999, pp. 179-186

Abstract

The neuroprotective activity of the non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist GYKI-52466 (1-[4-aminophenyl]-4-methyl-7,8-methylene-dioxy-5H-2,3-benzodiazepine HCl; EGIS-8159) was studied in the gerbil bilateral carotid occlusion (BCO) model of globalischemia. Drug effect on hippocampal CA1 neuronal loss, hypermotility, andcognitive deficit (decrease in spontaneous alternation (SA) behaviour in the Y-maze) induced by 5-min or 3-min BCO were measured. GYKI-52466 was administered at 4 x 15 mg/kg intraperitoneal (i.p.) doses 30, 45, 60, and 75 min following surgery. The competitive AMPA antagonist NBQX (2,3-dihidroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline) applied at 3 x 30 mg/kg i.p. doses 60, 70, and 85 min after reperfusion was also tested for comparison. Both compounds showed weak and non-significant effects on 5-min BCO-induced changes in all the three variables. However, following 3-min ischemia GYKI-52466and NBQX produced significant inhibition (49% and 48%, respectively) on CA1 cell loss. Moreover, GYKI-52466, but not NBQX, significantly inhibited the 8-min ischemia induced hypermotility and decrease in SA. At their neuroprotective doses, both compounds caused longlasting (min. 8 h) hypothermia ingerbils. GYKI-52466 induced much higher decrease in body temperature (6 degrees C at peak level) than NBQX did (2 degrees C at peak level). Administration of 4 x 10 mg/kg i.p. chlorpromazine to gerbils 15 min before and 0, 15, and 30 min after 3-min BCO resulted in considerable hypothermia (5.5 degrees C peak effect, 8 h duration), but no protective action of the compoundon CA1 cell loss and hypermotility was observed. However, chlorpromazine inhibited the ischemia-induced cognitive impairment. The results suggest that drug-induced hypothermia may differentially influence the histological and the behavioural outcomes of ischemic intervention. (C) 1999 Elsevier Science Inc.

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Documento generato il 06/04/20 alle ore 23:44:07