{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:58:05Z","timestamp":1790675885228,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010162204"],"award-info":[{"award-number":["PJT\u2010162204"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Temporal lobe epilepsy with hippocampal sclerosis (TLE\u2010HS+) is a common and often refractory form of human epilepsy. In the hippocampus, the neurotoxin stable substance P\u2010saporin (SSP\u2010SAP) targets hilar inhibitory interneurons and has been used to determine whether hilar neuron loss in an otherwise normal brain is sufficient to initiate the epileptogenic process. We determined the time course of SSP\u2010SAP\u2010induced epileptogenesis, as well as the loss of principal cells and astrogliosis, two defining features of TLE\u2010HS+.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We started with 70\u2010day\u2010old male and female Sprague Dawley rats and injected SSP\u2010SAP into four unilateral sites along the longitudinal axis of the rat dentate gyrus. We determined how long SSP\u2010SAP is detectably present in inhibitory interneurons and then analyzed the electroencephalographic characteristics and behavioral expression of the \u201creactive\u201d seizures that developed several days after SSP\u2010SAP injection. We then quantified the number of self\u2010generated 7\u2010Hz epileptiform events over 3\u2009months. Finally, we counted the numbers of principal cells and astrocytes up to 2\u2009months postinjection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SSP\u2010SAP was internalized within 2\u2009h after injection and was immunocytochemically undetectable by 5\u2009days. Rats exhibited spontaneous electrographic and behavioral reactive seizures between days 4 and 6 after SSP\u2010SAP injection, with most seizures having a Racine score of either 1 or 2. After the early seizures had abated, the number and duration of self\u2010generated 7\u2010Hz epileptiform events, which were associated with behavioral arrest, progressively increased over the 3\u2010month observation period, indicating epileptogenesis. We also observed the progressive loss of CA1 and CA3 neurons and the progressive increase in astrocytes over time, two defining features of HS, a common pathological observation in TLE patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>This study confirms that the SSP\u2010SAP model reproduces the defining features of human TLE and that a primary, selective, and longitudinally extensive \u03b3\u2010aminobutyric acidergic defect is sufficient to trigger epileptogenesis that results in TLE\u2010HS+.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70322","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T08:56:22Z","timestamp":1780304182000},"page":"4978-4992","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modeling temporal lobe epilepsy with hippocampal sclerosis in rats using the selective neurotoxin stable substance P\u2010saporin"],"prefix":"10.1002","volume":"67","author":[{"given":"Srijal","family":"Gupta","sequence":"first","affiliation":[{"name":"Hotchkiss Brain Institute University of Calgary  Calgary Alberta Canada"},{"name":"Department of Cell Biology and Anatomy University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell T.","family":"Kesler","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute University of Calgary  Calgary Alberta Canada"},{"name":"Department of Cell Biology and Anatomy University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morris H.","family":"Scantlebury","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute University of Calgary  Calgary Alberta Canada"},{"name":"Alberta Children's Hospital Research Institute University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6231-3171","authenticated-orcid":false,"given":"Robert S.","family":"Sloviter","sequence":"additional","affiliation":[{"name":"Neuroscience Institute Morehouse School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8462-355X","authenticated-orcid":false,"given":"G. 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