PNQX (9-methyl-amino-6-nitro-hexahydro-benzo(F)quinoxalinedione) is a selective
AMPA antagonist with demonstrated
neuroprotective effects in focal
ischemia in rats. Here we report corresponding effects in mouse hippocampal slice cultures subjected to
oxygen and
glucose deprivation (OGD) and in transient global
cerebral ischemia in gerbils. For in vitro studies, hippocampal slice cultures derived from 7-day-old mice and grown for 14 days, were submersed in
oxygen-
glucose deprived medium for 30 min and exposed to PNQX for 24 h, starting together with OGD, immediately after OGD, or 2 h after OGD. For comparison, other cultures were exposed to the
NMDA antagonist
MK-801 using the same protocol. Both PNQX and
MK-801 displayed significant
neuroprotective effects in all hippocampal subfields when present during and after OGD. When added just after OGD, only PNQX retained some
neuroprotective effect. When added 2 h after OGD neither PNQX nor
MK-801 had an effect. Transient global
cerebral ischemia was induced in Mongolian gerbils by occlusion of both common carotid arteries for 4.5 min, with PNQX (10 mg/kg) being injected i.p. 30, 60 and 90 min after the insult. Subsequent analysis of brain sections stained for the neurodegeneration marker
Fluoro-Jade B and immunostained for the astroglial marker
glial fibrillary acidic protein revealed a significant PNQX-induced decrease in neuronal cell death and astroglial activation. We conclude that, PNQX provided neuroprotection against both global
cerebral ischemia in gerbils in vivo and
oxygen-
glucose deprivation in mouse hippocampal slice cultures.