Effects of the AMPA-receptor antagonist, NBQX, on neuron loss in dentate hilus of the hippocampal formation after 8, 10, or 12 min of cerebral ischemia in the rat.
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.
Hu
P
P
Institute of Neuropathology, University of Copenhagen, Denmark.
Diemer
N H
NH
Bruhn
T
T
Johansen
F F
FF
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008026:Ligation; D008297:Male; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D011810:Quinoxalines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D012769:Shock / Q000150:complications; D013004:Somatostatin / Q000032:analysis; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D013004:Somatostatin