TRAUMATIC NEURONAL INJURY IN CORTICAL CELL-CULTURE IS ATTENUATED BY 21-AMINOSTEROIDS

The effect of the 21-aminosteroids U74500A and U74389F, alone and in c ombination with the NMDA receptor antagonist MK-801, on traumatic neur onal injury was quantitatively assessed in murine neocortical cell cul tures. Consistent with prior observations, a mechanical insult to the culture monolayer resulted in widespread neuronal death over the follo wing 24 h. Treatment with either U74500A or U74389F provided moderate protection, reducing neuronal death as measured by lactate dehydrogena se release by 25-50%. This effect was most consistent when these agent s were preincubated for 2 h prior to injury. Combined treatment with a 21-aminosteroid plus the NMDA receptor antagonist MK-801 reduced inju ry more than either drug alone. Approximately 40% of the neuronal deat h occurring in the presence of MK-801 was blocked by concomitant treat ment with 10 mu M U74500A or U74389F. These results suggest that free radicals may contribute to cell death in this in vitro model of trauma tic neuronal injury.