Repeated hypoxic episodes induce seizures and alter hippocampal network activities in mice

We examined intra-cranial electroencephalographic activity in a mouse model of global hypoxia in an attempt to explore the pathophysiology underlying hypoxic seizures. Mice between the ages of 22 and 41 days underwent repeated hypoxic challenges, and their behavioral and electroencephalographic activities were monitored continuously before, during and after the challenge. We found that the animals exhibited convulsive behaviors during the hypoxic challenge, but hippocampal/cortical electrographic ictal discharges were recognizable only after the repeated hypoxic challenge. When examined in hippocampal slices in vitro, the post-hypoxic hippocampal circuit was hyper-excitable and had a higher propensity than the control to generate repetitive excitatory field potentials. We postulate that an ictogenic process develops after an initial hypoxic challenge rendering an increase of seizure susceptibility to recurrent hypoxic insults.