Abstracts

RATIONALE: Prolonged seizures can cause brain damage in all animals regardless of age. However, the degree of seizure-induced brain damage is highly age-dependent. The mechanisms underlying the decreased vulnerability of the immature brain to seizure-induced brain damage remain unknown. It is hypothesized that mitochondrial oxidative stress is an important underlying mechanism by which ageing influences the occurrence of seizure-induced brain damage.
METHODS: Using aconitase inactivation and 8-hyroxyguanosine (8OhdG) as indices of steady-state mitochondrial superoxide production and oxidative DNA damage respectively, we asked whether kainate-induced seizures in developing (postnatal days 12 to 21) and adult (postnatal days 30 to 60) animals increased oxidative stress and whether this correlated with cell damage.
RESULTS: Mitochondrial aconitase inactivation and 8OHdG formation were increased in the hippocampus and piriform cortex by kainate administration in adult (postnatal days 30 to 60), but not young rats (postnatal days 12 and 21). The absence of oxidative injury to cellular macromolecules, correlated with the minimal neuronal loss and microglial activation observed in the young animals. The absence of mitochondrial oxidative stress in young animals was not due to a selective induction of MnSOD, a critical mitochondrial antioxidant enzyme.
CONCLUSIONS: The age-dependent increase in mitochondrial superoxide production and oxidative DNA damage, suggests that oxidative mechanisms play a key role in the resistance of the immature brain to seizure-induced neuronal death. The inability of the developing brain to succumb to mitochondrial oxidative injury following seizures may render it resistant to seizure-induced brain damage.
[Supported by: Parents Against Childhood Epilepsy (PACE)]