Treatment with an AMPA antagonist 12 hours following severe normothermic forebrain ischemia prevents CA1 neuronal injury.
The neuroprotective effects of 2,3-dihydroxy-6-nitro-7- sulfamoylbenzo(f)quinoxaline (NBQX), GYKI 52466, and MK-801 were tested following severe forebrain ischemia. Wistar rats were subjected to 10 min of normothermic ischemia and reperfused for 7 days. Necrotic hippocampal CA1 neurons were counted and expressed as a percentage (mean +/- SD). In Experiment 1, saline-treated rats sustained 81 +/- 20% damage to dorsal CA1. Rats given NBQX 30 mg/kg i.p. x3 lost 21 +/- 27% (p < 0.01). Neither MK-801 1 mg i.p. x3 alone, nor in combination with the cytoprotective dose of NBQX protected CA1, with 83 +/- 18 and 54 +/- 34% damage, respectively (NS). Giving NBQX 90 mg/kg i.v. did not protect cells (94 +/- 5%) and resulted in nephrotoxicity. In Experiment 2, rats were given saline or three doses of NBQX 30 mg/kg i.p. immediately at reperfusion (RP) or after a 6-, 12-, or 24-h delay. Saline-treated rats suffered 79 +/- 16% injury. NBQX given immediately resulted in 17 +/- 17% injury, and even if treatment was delayed by either 6 or 12 h, there was marked protection with only 27 +/- 32 and 25 +/- 17% injury, respectively (all p < 0.01). Delaying the initiation of treatment to 24 h was not successful, resulting in 50 +/- 28% injury (NS). In Experiment 3, saline-treated rats lost 81 +/- 19% of CA1 cells, while those given GYKI 52466 10 mg/kg i.p. x5 starting immediately following RP lost 80 +/- 14%.(ABSTRACT TRUNCATED AT 250 WORDS)
Li
H
H
University of Ottawa, Ottawa Civic Hospital, Ontario, Canada.
Buchan
A M
AM
D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000627:therapeutic use; D001927:Brain Diseases / Q000209:etiology / Q000517:prevention & control*; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D006624:Hippocampus / Q000473:pathology*; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000473:pathology; D016548:Prosencephalon / Q000098:blood supply; D011810:Quinoxalines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors*
D014151:Anti-Anxiety Agents; D011810:Quinoxalines; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines; D016291:Dizocilpine Maleate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid