Rapid and slow swelling during hypoxia in the CA1 region of rat hippocampal slices

The role of swelling in hypoxic/ischemic neuronal injury is incompletely un derstood. We investigated the extent and time course of cell swelling durin g hypoxia, and recovery of cell volume during reoxygenation, in the CAI reg ion of rat hippocampal slices in vitro. Cell swelling was measured opticall y and compared with simultaneous measurements of the extracellular DC poten tial, extracellular [K+], and synaptic transmission in the presence and abs ence of hypoxic depolarization. Hypoxia-induced swelling consisted of rapid and/or slow components. Rapid swelling was observed frequently and always occurred simultaneously with hypoxic depolarization. Additionally, rapid sw elling was followed by a prolonged phase of swelling that was similar to 15 times slower. Less frequently, slow swelling occurred independently, witho ut either hypoxic depolarization or a preceding rapid swelling. For slices initially swelling rapidly, recovery of both cell volume and the slope of f ield excitatory postsynaptic potentials were best correlated with the durat ion of hypoxia (r = 0.77 and 0.87, respectively). This was also the case fo r slices initially swelling slowly (r = 0.70 and 0.58, respectively). In co ntrast, the degree of recovery of cell volume was the same at 30 or 60 min of reoxygenation, indicating that prolonging the duration of reoxygenation within these limits was ineffective in improving recovery. Spectral measure ments indicated that the hypoxia-induced changes in light transmittance wer e related to changes in cell volume and not changes in the oxidation state of mitochondrial cytochromes. The persistent impairment of synaptic transmi ssion in slices swelling slowly (i.e., without hypoxic depolarization) indi cates that swelling may play a role in this injury and that hypoxic depolar ization is not required. Additionally, the correlation between the degree o f recovery of cell volume and the degree of recovery of synaptic transmissi on during reoxygenation supports a role for swelling in hypoxic neuronal in jury.