ANATOMICAL AND ELECTROPHYSIOLOGICAL STUDIES OF AN ANIMAL MODEL OF TEMPORAL LOBE EPILEPSY WITH CLASSIC HIPPOCAMPAL SCLEROSIS

Persistent Link:
http://hdl.handle.net/10150/194204
Title:
ANATOMICAL AND ELECTROPHYSIOLOGICAL STUDIES OF AN ANIMAL MODEL OF TEMPORAL LOBE EPILEPSY WITH CLASSIC HIPPOCAMPAL SCLEROSIS
Author:
Norwood, Braxton
Issue Date:
2009
Publisher:
The University of Arizona.
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.
Embargo:
Dissertation Not Available (per Author's Request) / University of Arizona affiliates can find this item in the ProQuest Dissertations and Theses Full-text Database
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.
Type:
text; Electronic Dissertation
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Medical Pharmacology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Sloviter, Robert S

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleANATOMICAL AND ELECTROPHYSIOLOGICAL STUDIES OF AN ANIMAL MODEL OF TEMPORAL LOBE EPILEPSY WITH CLASSIC HIPPOCAMPAL SCLEROSISen_US
dc.creatorNorwood, Braxtonen_US
dc.contributor.authorNorwood, Braxtonen_US
dc.date.issued2009en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © 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.en_US
dc.description.releaseDissertation Not Available (per Author's Request) / University of Arizona affiliates can find this item in the ProQuest Dissertations and Theses Full-text Databaseen_US
dc.description.abstractIn 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.en_US
dc.description.noteDissertation restricted per author's request, September 7, 2012 / KCen_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineMedical Pharmacologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorSloviter, Robert Sen_US
dc.contributor.committeememberBarnes, Carol A.en_US
dc.contributor.committeememberKudrimoti, Hemant S.en_US
dc.contributor.committeememberPorreca, Franken_US
dc.contributor.committeememberVanderah, Todd W.en_US
dc.identifier.proquest10772en_US
dc.identifier.oclc659753614en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.