High oxygen tension leads to acute cell death in organotypic hippocampal slice cultures

Increased oxygen tension in the central nervous system can be of relevance In different clinical situations, e.g. hyperbaric oxygen treatment during r esuscitation of newborns in asphyxia as well as during seizures in children and adults where the supply of oxygen to tissue is increased by elevated c erebral blood flow. We focused on changes in neuronal tissue by investigati ng the impact of different oxygen tensions on juvenile rat hippocampal slic e cultures using extracellular field potential recordings and propidium iod ide (PI) staining for cell death determination. Slice cultures were prepare d following the Stoppini technique (postnatal days 6-8). Electrophysiologic al responses in area CA1 to hilar stimulation were recorded every 15 min af ter an initial equilibration period of 60 min. Slice cultures maintained in 95% oxygen showed a 53% (S.E.M. = 17%; n = 10) run-down in amplitudes of t he evoked responses over the observation time course of 90 min. In contrast , slice cultures maintained in 19% oxygen showed no run-down in amplitudes (S.E.M. = 9%; n = 18). PI staining of the slice cultures carried out immedi ately after the electrophysiological measurements indicated a dramatic cell death rate in the high oxygen tension group compared to those maintained i n 19% oxygen. Interestingly, epileptiform activity (seizure-like events, sp reading depression-like events) occurred in some slice cultures dependent o n oxygen tension. Altered paired-pulse index of evoked responses suggests a loss of GABAergic function, especially in the 95% oxygen tension group. Th ese results demonstrate a high sensitivity to oxygen in juvenile rat hippoc ampal slice cultures, in contrast to acutely prepared juvenile and adult ra t hippocampal slices. (C) 2001 Elsevier Science B.V. All rights reserved.