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

• Published in: Neuroscience Vol. 171; no. 2; pp. 556 - 565
• Main Authors: Jimenez-Mateos, E.M, Mouri, G, Conroy, R.M, Henshall, D.C
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-12-2010; Elsevier
• Subjects: Amygdala; Animals; Biological and medical sciences; Brain injury; CA3 Region, Hippocampal - pathology; Cell Count; Cell Death; Cytoprotection; epileptogenesis; Fundamental and applied biological sciences. Psychology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; hippocampal sclerosis; Kainic Acid; Male; Medical sciences; Mice; Mice, Inbred C57BL; mossy fiber sprouting; Mossy Fibers, Hippocampal - pathology; Nervous system (semeiology, syndromes); Neurology; Neurons - pathology; Neuropeptide Y - metabolism; preconditioning; Seizures - pathology; Seizures - physiopathology; Seizures - prevention & control; status epilepticus; Status Epilepticus - chemically induced; Status Epilepticus - physiopathology; Status Epilepticus - prevention & control; Synapses - pathology; Time Factors; Vertebrates: nervous system and sense organs; PBS; cornu ammonis; temporal lobe epilepsy; kainic acid; hippocampal sclerosis; EEG; neuropeptide Y; mossy fiber sprouting; glial fibrillary acid protein; phosphate-buffered saline; TLE; electroencephalogram; preconditioning; GFAP; status epilepticus; fluoro-jade B; epileptogenesis; KA; NPY; MFS; CA; FJB; Neuropeptide Y; Mossy fiber; Neuroprotection; Nervous system diseases; Amygdala; Epilepsy; Rodentia; Central nervous system; Tolerance; Basal ganglion; Encephalon; Cerebral disorder; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; Kainic acid; Status epilepticus; Preconditioning; Hippocampus
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.09.003

Abstract 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