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 patte rn. Consistent with prior observations, neurons adjacent to a tear dev eloped immediate swelling, and then went on to degenerate over the nex t several hours. Delivery of multiple tears produced enough cell death that measurable levels of lactate dehydrogenase accumulated in the ba thing medium 24 h later, correlating well with the extent of cell deat h 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 mu M CNQX also attenuated neuronal degeneration, but t his neuroprotective effect was likely due to attenuation of NMDA recep tor-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 m odest neuroprotective effects; either dihydropyridine when combined wi th MK-801 reduced injury more than MK-801 alone. These results suggest that traumatic neuronal death in this in vitro model is mediated in p art by excessive activation of NMDA receptors, and in part by mechanis ms sensitive to high concentrations of dihydropyridines, but not by AM PA/kainate receptors.