Brain research bulletin
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Brain research bulletin · Oct 1999
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.
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-benzodia zep ine HCI; EGIS-8159) was studied in the gerbil bilateral carotid occlusion (BCO) model of global ischemia. Drug effect on hippocampal CA1 neuronal loss, hypermotility, and cognitive 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. ⋯ 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 compound on 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.