DELAYED NEURONAL INJURY-INDUCED BY SUBLETHAL NMDA EXPOSURE IN THE HIPPOCAMPAL SLICE

Stroke produces neuronal death by two general processes which differ i n their temporal course. Acute neuronal death occurs within minutes, w hile delayed neuronal death evolves within 24 h. To better examine mec hanisms of delayed death, we developed a new in vitro model of delayed neuronal injury using extended electrophysiological recordings in pai red hippocampal slices. We exposed one hippocampal slice of each pair to 10 mu M N-methyl-D-aspartate (NMDA) until the orthodromic CA1 PS di sappeared. Thereafter, NMDA-treated slices regained near full recovery of PS amplitude within one hour. However, 10 h later, NMDA-treated sl ices demonstrated a rapid decline in PS amplitude of 82% +/- 15. CA1 o rthodromic evoked PS was lost completely at an average 12.4 +/- 1.6 h after NMDA exposure. This sudden loss of response contrasted with pair ed, untreated slices, where CA1 PS could be elicited for 22.6 +/- 4.0 h (P < 0.05). Treatment with 10 mM MgCl2 begun after NMDA exposure and continued for 35 min, prevented delayed loss of CA1 orthodromic PS, w hich then could be elicited for 20.3 +/- 2.1 h. These results indicate that delayed injury can be evaluated using the hippocampal slice. The y also suggest that activation of NMDA receptors can induce delayed ne uronal injury in CA1 neurons, and that magnesium treatment after NMDA can prevent this injury.