Extended studies on the effect of glutamate antagonists on ischemic CA-1 damage.

Abstract

Glutamate receptors are numerous on the ischemia vulnerable CA-1 pyramidal cells. Postischemic use of the AMPA antagonist NBQX has shown up to 80% protection against cell death. Three aspects of this were studied: In the first study, male Wistar rats were given NBQX (30 mg/kg x 3) either 20 hours or immediately (0 h) before 12 min of 4-vessel occlusion with hypotension. After six days of reperfusion comparison with an untreated group showed almost full protection in the 0 h group (4% cell loss, p < 0.001) but only slight protection in the 20 h group (62% cell loss, p < 0.05). After 12 min of ischemia in the present model, eosinophilic CA-1 cells are seen from day 2 on. Since there could be a late, deleterious calcium influx via NMDA receptors, one group of ischemic rats was given MK-801 (5 mg/kg i.p.) 24 hours after ischemia. However, quantitation 6 days later of remaining CA-1 cells showed no protection. In the third study referred here, two groups of ischemic rats were given NBQX (30 mg/kg x 3) immediately after ischemia. The groups survive for six and 21 days, respectively. Counting of CA-1 pyramidal cells showed an equal, significant protection in both groups (approx 20% cell loss).

• Authors: N H Diemer, T Balchen, T Bruhn, T Christensen, I Vanicky, M Nielsen, F F Johansen
• Journal: Acta neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 66 Pg. 73-5 ( 1996) ISSN: 0065-1419 [Print] Austria
• PMID: 8780801 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Antagonists
• Quinoxalines
• Receptors, AMPA
• Receptors, N-Methyl-D-Aspartate
• 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
• Glutamic Acid
• Dizocilpine Maleate

Topics

• Animals
• Brain Damage, Chronic (pathology)
• Brain Ischemia (pathology)
• Brain Mapping
• Dizocilpine Maleate (pharmacology)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Excitatory Amino Acid Antagonists (pharmacology)
• Glutamic Acid (physiology)
• Hippocampus (blood supply, drug effects, pathology)
• Male
• Neurons (drug effects, pathology)
• Premedication
• Quinoxalines (pharmacology)
• Rats
• Rats, Wistar
• Receptors, AMPA (antagonists & inhibitors, physiology)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors, physiology)