{"id":{"repo_id":"arizona-thes","oai_identifier":"oai:repository.arizona.edu:10150/194204"},"canonical_url":"https://search.dev.ndltd.org/etd/arizona-thes/oai:repository.arizona.edu:10150/194204","repository":{"repo_id":"arizona-thes","name":"University of Arizona","base_url":"https://repository.arizona.edu/oai/request"},"display":{"title":"ANATOMICAL AND ELECTROPHYSIOLOGICAL STUDIES OF AN ANIMAL MODEL OF TEMPORAL LOBE EPILEPSY WITH CLASSIC HIPPOCAMPAL SCLEROSIS","abstract":"In mesial temporal lobe epilepsy, seizures often arise from an atrophic hippocampus exhibiting a characteristic pattern of hippocampal neuron loss called \"classic hippocampal sclerosis.\" No single injury has reproduced this extensive neuron loss experimentally, suggesting that hippocampal sclerosis may be an \"endstage\" pathology caused by an initial insult plus years of spontaneous seizures. We developed an experimental paradigm to test the alternate hypothesis that the extensive hippocampal pathology and limited extrahippocampal pathology typically seen in patients is caused by a single prolonged episode of hippocampal excitation insufficiently intense to cause convulsive status epilepticus (SE). Two daily 30 minute-long episodes of perforant pathway stimulation in awake Sprague-Dawley rats increased granule cell paired-pulse inhibition and truncated epileptiform discharges evoked during 8 hours of subsequent stimulation, thus avoiding the lethal SE that identical stimulation evoked in naive animals. Similarly, 8 hours of less intense stimulation in Long-Evans rats, which are relatively resistant to developing convulsive SE, produced hippocampal seizure discharges, but not convulsive SE. Both paradigms produced classic hippocampal sclerosis and limited extrahippocampal pathology without any clinical indication during stimulation that an injury was being inflicted. Spontaneous hippocampal-onset seizures began ~3 weeks post-injury, before the development of hippocampal atrophy, demonstrated by sequential magnetic resonance imaging. These results indicate that classic hippocampal sclerosis is produced immediately by a single episode of clinically \"cryptic\" temporal lobe excitation of a particular intensity and duration. Epileptogenic injuries may involve focal excitatory disturbances of hippocampal function that frequently go undetected at the time of initial injury.","abstract_html":"In mesial temporal lobe epilepsy, seizures often arise from an atrophic hippocampus exhibiting a characteristic pattern of hippocampal neuron loss called "classic hippocampal sclerosis." No single injury has reproduced this extensive neuron loss experimentally, suggesting that hippocampal sclerosis may be an "endstage" pathology caused by an initial insult plus years of spontaneous seizures. We developed an experimental paradigm to test the alternate hypothesis that the extensive hippocampal pathology and limited extrahippocampal pathology typically seen in patients is caused by a single prolonged episode of hippocampal excitation insufficiently intense to cause convulsive status epilepticus (SE). Two daily 30 minute-long episodes of perforant pathway stimulation in awake Sprague-Dawley rats increased granule cell paired-pulse inhibition and truncated epileptiform discharges evoked during 8 hours of subsequent stimulation, thus avoiding the lethal SE that identical stimulation evoked in naive animals. Similarly, 8 hours of less intense stimulation in Long-Evans rats, which are relatively resistant to developing convulsive SE, produced hippocampal seizure discharges, but not convulsive SE. Both paradigms produced classic hippocampal sclerosis and limited extrahippocampal pathology without any clinical indication during stimulation that an injury was being inflicted. Spontaneous hippocampal-onset seizures began ~3 weeks post-injury, before the development of hippocampal atrophy, demonstrated by sequential magnetic resonance imaging. These results indicate that classic hippocampal sclerosis is produced immediately by a single episode of clinically "cryptic" temporal lobe excitation of a particular intensity and duration. Epileptogenic injuries may involve focal excitatory disturbances of hippocampal function that frequently go undetected at the time of initial injury.","abstract_has_math":false,"creators":["Norwood, Braxton"],"institution":"The University of Arizona.","degree_name":"Ph.D.","degree_level":"doctoral","degree_discipline":"Medical Pharmacology","degree_department":null,"school":null,"contributors":[],"advisors":["Sloviter, Robert S"],"committee_chairs":[],"committee_members":["Barnes, Carol A.","Kudrimoti, Hemant S.","Porreca, Frank","Vanderah, Todd W."],"year":2009,"date_issued":"2009","date_published":"2009","updated_at":"2026-07-24T00:55:59Z","subjects":[],"languages":["EN"],"rights":["Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. 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Spontaneous hippocampal-onset seizures began ~3 weeks post-injury, before the development of hippocampal atrophy, demonstrated by sequential magnetic resonance imaging. These results indicate that classic hippocampal sclerosis is produced immediately by a single episode of clinically \"cryptic\" temporal lobe excitation of a particular intensity and duration. Epileptogenic injuries may involve focal excitatory disturbances of hippocampal function that frequently go undetected at the time of initial injury."]},{"key":"dc:title","label":"Title","values":["ANATOMICAL AND ELECTROPHYSIOLOGICAL STUDIES OF AN ANIMAL MODEL OF TEMPORAL LOBE EPILEPSY WITH CLASSIC HIPPOCAMPAL SCLEROSIS"]}]}],"canonical_facts":{"dc:contributor.advisor":["Sloviter, Robert S"],"dc:contributor.committeemember":["Barnes, Carol A.","Kudrimoti, Hemant S.","Porreca, Frank","Vanderah, Todd W."],"dc:creator":["Norwood, Braxton"],"dc:date.accessioned":["2011-12-05T22:23:18Z"],"dc:date.available":["2011-12-05T22:23:18Z"],"dc:date.issued":["2009"],"dc:description.abstract":["In mesial temporal lobe epilepsy, seizures often arise from an atrophic hippocampus exhibiting a characteristic pattern of hippocampal neuron loss called \"classic hippocampal sclerosis.\" No single injury has reproduced this extensive neuron loss experimentally, suggesting that hippocampal sclerosis may be an \"endstage\" pathology caused by an initial insult plus years of spontaneous seizures. We developed an experimental paradigm to test the alternate hypothesis that the extensive hippocampal pathology and limited extrahippocampal pathology typically seen in patients is caused by a single prolonged episode of hippocampal excitation insufficiently intense to cause convulsive status epilepticus (SE). Two daily 30 minute-long episodes of perforant pathway stimulation in awake Sprague-Dawley rats increased granule cell paired-pulse inhibition and truncated epileptiform discharges evoked during 8 hours of subsequent stimulation, thus avoiding the lethal SE that identical stimulation evoked in naive animals. Similarly, 8 hours of less intense stimulation in Long-Evans rats, which are relatively resistant to developing convulsive SE, produced hippocampal seizure discharges, but not convulsive SE. Both paradigms produced classic hippocampal sclerosis and limited extrahippocampal pathology without any clinical indication during stimulation that an injury was being inflicted. Spontaneous hippocampal-onset seizures began ~3 weeks post-injury, before the development of hippocampal atrophy, demonstrated by sequential magnetic resonance imaging. These results indicate that classic hippocampal sclerosis is produced immediately by a single episode of clinically \"cryptic\" temporal lobe excitation of a particular intensity and duration. Epileptogenic injuries may involve focal excitatory disturbances of hippocampal function that frequently go undetected at the time of initial injury."],"dc:identifier.uri":["http://hdl.handle.net/10150/194204"],"dc:language.iso":["EN"],"dc:publisher":["The University of Arizona."],"dc:rights":["Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author."],"dc:title":["ANATOMICAL AND ELECTROPHYSIOLOGICAL STUDIES OF AN ANIMAL MODEL OF TEMPORAL LOBE EPILEPSY WITH CLASSIC HIPPOCAMPAL SCLEROSIS"],"dc:type":["text","Electronic Dissertation"],"thesis:degree_discipline":["Medical Pharmacology","Graduate College"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Arizona"]},"updated_at":"2026-07-24T00:55:59Z"}