EPILEPTIC TOLERANCE IS ASSOCIATED WITH ENDURING NEUROPROTECTION AND UNCOUPLING OF THE RELATIONSHIP BETWEEN CA3 DAMAGE, NEUROPEPTIDE Y REARRANGEMENT AND SPONTANEOUS SEIZURES FOLLOWING INTRA-AMYGDALA KAINIC ACID-INDUCED STATUS EPILEPTICUS IN MICE

Brief, non harmful seizures can activate endogenous protective programmes which render the brain resistant to damage caused by prolonged seizure episodes Whether protection in epileptic tolerance is long lasting or influences the subsequent development of epilepsy is uncertain Presently we investigated the relationship between hippocampal pathology, neuropeptide Y rearrangement and spontaneous seizures in sham and seizure-preconditioned mice after status epilepticus induced by intra amygdala kainate Seizure induced neuronal death at 24 h was significantly reduced in the ipsilateral hippocampal CA3 and hilus of tolerance mice compared to sham-preconditioned animals subject to status epilepticus Damage to the CA3 hilus remained reduced in tolerance mice 21 days post status In sham preconditioned mice subject to status epilepticus correlative statistics showed there was a strong inverse relationship between CA3, but not hilar, neuron counts and the number of spontaneous seizures A strong positive association was also found between neuropeptide Y score and spontaneous seizure count in these mice In contrast, there was no significant association between spontaneous seizure count and CA3 neuron loss or neuropeptide Y rearrangement in the tolerance mice These data show that tolerance conferred neuro protection is long lasting and that tolerance disrupts the nor mal association between CA3 damage, synaptic rearrangement and occurrence of spontaneous seizures in this model (C) 2010 IBRO Published by Elsevier Ltd All rights reserved