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 neuroprotection is long-lasting and that tolerance disrupts the normal association between CA3 damage, synaptic rearrangement and occurrence of spontaneous seizures in this model.
Jimenez-Mateos
E M
EM
Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
Mouri
G
G
Conroy
R M
RM
Henshall
D C
DC
D000679:Amygdala; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000473:pathology*; D002452:Cell Count; D016923:Cell Death; D019610:Cytoprotection; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019599:Mossy Fibers, Hippocampal / Q000473:pathology; D009474:Neurons / Q000473:pathology; D009478:Neuropeptide Y / Q000378:metabolism*; D012640:Seizures / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D013569:Synapses / Q000473:pathology; D013997:Time Factors
D009478:Neuropeptide Y; D007608:Kainic Acid