Non-NMDA but not NMDA blockade at deep prepiriform cortex protects against hippocampal cell death in status epilepticus.
The present study investigates the role of pharmacologic blockade of NMDA (N-methyl-D-aspartate) and non-NMDA receptors at deep prepiriform cortex (area tempestas, AT) in neuronal injury during prolonged seizures in rat. Status epilepticus was induced by intravenous kainate (15 mg/kg) and neuronal death was assessed in hippocampal CA3 sector 72 h following status epilepticus. Unilateral equimolar microinjections of 2-amino-7-phosphonoheptanoic acid (AP-7), an NMDA receptor antagonist, or 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), a non-NMDA receptor antagonist, into AT were given prior to kainate administration. Counts of surviving cells in CA3 ipsilateral to NBQX-injected AT were significantly greater than on the contralateral control-side, but no significant difference between the AP-7-injected and saline-injected side was found. These results indicate that neurotransmission via non-NMDA receptors is more important than that via NMDA receptors at AT in the genesis of neuronal injury in hippocampus during kainate-induced status epilepticus.
Kawaguchi
K
K
Department of Neurology, University of Pittsburgh, PA 15213, USA.
Simon
R P
RP
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009833:Olfactory Pathways / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015203:Reproducibility of Results; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid; D007608:Kainic Acid