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

Neuroscience. 2010 Dec 1;171(2):556-65. doi: 10.1016/j.neuroscience.2010.09.003. Epub 2010 Sep 17.


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 neuroprotection is long-lasting and that tolerance disrupts the normal association between CA3 damage, synaptic rearrangement and occurrence of spontaneous seizures in this model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala
  • Animals
  • CA3 Region, Hippocampal / pathology*
  • Cell Count
  • Cell Death
  • Cytoprotection
  • Kainic Acid*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mossy Fibers, Hippocampal / pathology
  • Neurons / pathology
  • Neuropeptide Y / metabolism*
  • Seizures / pathology
  • Seizures / physiopathology
  • Seizures / prevention & control*
  • Status Epilepticus / chemically induced
  • Status Epilepticus / physiopathology
  • Status Epilepticus / prevention & control*
  • Synapses / pathology
  • Time Factors


  • Neuropeptide Y
  • Kainic Acid