The alpha-amino-3-hydroxy-5-methyl-4-isoxazole (
AMPA) receptor antagonist,
2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (
NBQX), offers protection to hippocampal CA1 pyramidal cells after short episodes of
transient cerebral ischemia. Besides CA1 pyramidal cells, neurons containing
somatostatin (SS) and located in the dentate hilus of the hippocampal formation are lost after
cerebral ischemia. We studied the protective effects of
NBQX on SS neurons in the hilus and on hippocampal CA1 pyramidal cells following 8, 10, or 12 min of four-vessel occlusion
ischemia during systemic
hypotension.
NBQX was administered 3 x 30 mg/kg at 0, 10, and 25 after induction of
ischemia or
sham, and all rats survived for 7 days.
NBQX given to control rats without
ischemia had no influence on number or morphology of hilar SS neurons and CA1 pyramidal cells. After 8 min of
ischemia,
NBQX prevented loss of hilar SS neurons. After 10 and 12 min of
ischemia,
NBQX had no significant effects on loss of SS neurons in the dentate hilus. However, in all ischemic groups,
NBQX significantly reduced loss of CA1 pyramidal cells as compared to control rats. This
neuroprotective effect decreased gradually and significantly as the time of
ischemia increased. Our results support the observation that SS neurons in hilus are among the most
ischemia-vulnerable neurons in the brain. We found that administration of
NBQX in generally accepted dosages can protect the rapidly dying SS neurons in hilus from only brief episodes of
ischemia.