The effects of pilocarpine-induced status epilepticus on oxidative stress/damage in developing animals

Pilocarpine (PC), a muscarinic receptor agonist, is used for the induction of experimental models of status epilepticus (SE) for studying the type of seizure-induced brain injury and other neuropathophysiological mechanisms of related disorder. PC was administered to day-old Taiwan Native Breeder chicks and induced severe prolonged seizures (PC + PS) and repeated seizures (PC + RS) during 4 h behavioral observations. Results showed that PC + PS group had excessive levels of reactive oxygen species (ROS) and malondialdehyde (MDA) production and lower activities of superoxide dismutase (SOD) and catalase (CAT) compared to the PC + RS group (p < 0.05). Neuronal death and single strand DNA were significantly increased in dissociated brain cells of PC + PS group compared to that in the PC + RS group (p < 0.01). Furthermore, a decrease in mitochondrial membrane potential (MMP) was observed in PC + PS group as compared with that in PC + RS group indicating neuronal mitochondrial dysfunction in PS group not in RS group. ROS, mitochondrial dysfunction and DNA damage played important roles in pathophysiology of the immature brain to prolonged-seizure-induced damage. A manifest result of depleted enzymatic antioxidants (SOD and CAT) was also contributed for the vulnerability of the neonatal brain to prolonged-seizure-induced oxidative damage. The replenishment of SOD and CAT activities might be useful in protecting brain against prolonged-seizure-induced neuronal death.