The effect of NMDA, AMPA/kainate, and calcium channel antagonists on traumatic cortical neuronal injury in culture.
A traumatic insult was delivered to murine cortical neuronal and glial cell cultures by tearing the cell layer with a stylet in a grid pattern. Consistent with prior observations, neurons adjacent to a tear developed immediate swelling, and then went on to degenerate over the next several hours. Delivery of multiple tears produced enough cell death that measurable levels of lactate dehydrogenase accumulated in the bathing medium 24 h later, correlating well with the extent of cell death as assessed by Trypan blue exclusion and cell counts. 50-75% of this trauma-induced cell death was blocked by the NMDA receptor antagonist MK-801. 10-100 microM CNQX also attenuated neuronal degeneration, but this neuroprotective effect was likely due to attenuation of NMDA receptor-mediated toxicity, since the more specific AMPA/kainate antagonist NBQX was ineffective. CNQX also did not augment the protective effect of MK-801. High concentrations of nimodipine or nifedipine produced modest neuroprotective effects; either dihydropyridine when combined with MK-801 reduced injury more than MK-801 alone. These results suggest that traumatic neuronal death in this in vitro model is mediated in part by excessive activation of NMDA receptors, and in part by mechanisms sensitive to high concentrations of dihydropyridines, but not by AMPA/kainate receptors.
Regan
R F
RF
Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19107.
Choi
D W
DW
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000293:injuries*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009553:Nimodipine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014343:Trypan Blue
D002121:Calcium Channel Blockers; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D009553:Nimodipine; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D007770:L-Lactate Dehydrogenase; D014343:Trypan Blue