Early hippocampal oxidative stress is a direct consequence of seizures in the rapid electrical amygdala kindling model.

Epilepsy is characterised by recurrent seizures, which are manifestations of aberrant cortical neuronal firing. It is unclear whether oxidative stress is a cause or consequence of seizure-related hippocampal neuronal loss or whether it occurs concomitantly with the initiation of cell death pathways. We utilised the rapid electrical amygdala kindling (REAK) model which does not induce cell death to examine early seizure-induced oxidative stress in wildtype and superoxide dismutase 2 (Sod2) +/- mice, which lack 50% of Sod2 activity and are therefore known to be more susceptible to mitochondrial oxidative stress. A significant increase in lipid peroxidation and superoxide production was noted in the hippocampi of wildtype mice and a more delayed response observed in Sod2 +/- mice at early time-points post-seizures, but protein carbonylation levels appeared unchanged. A 10-fold increase in superoxide production was seen in the Sod2 +/- CA2 neurons, indicating that Sod2 plays an important role in protecting the CA2 region of the hippocampus from seizure-induced free radical damage. Early hippocampal cell death was undetectable in wildtype or Sod2 +/- mice post-seizures. We were able to demonstrate that hippocampal oxidative stress occurred as a direct consequence of seizures rather than downstream of activation of cell death pathways. We were also able to show that this increase in oxidative stress was not sufficient to cause cell death within the time window investigated. Our data indicates that a possible upregulation of endogenous antioxidant activity might exist within selective hippocampal sectors in the Sod2 +/- mice that are as yet unknown.