{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:09:22Z","timestamp":1787724562381,"version":"build-2784847793"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T00:00:00Z","timestamp":1715990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["S10 RR027552"],"award-info":[{"award-number":["S10 RR027552"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS056872"],"award-info":[{"award-number":["R01 NS056872"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS062806"],"award-info":[{"award-number":["R01 NS062806"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P50 HD103525"],"award-info":[{"award-number":["P50 HD103525"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The mechanistic target of rapamycin (mTOR) pathway has been implicated in promoting epileptogenesis in animal models of acquired epilepsy, such as posttraumatic epilepsy (PTE) following traumatic brain injury (TBI). However, the specific anatomical regions and neuronal populations mediating mTOR's role in epileptogenesis are not well defined. In this study, we tested the hypothesis that mTOR activation in dentate gyrus granule cells promotes neuronal death, mossy fiber sprouting, and PTE in the controlled cortical impact (CCI) model of TBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An adeno\u2010associated virus (AAV)\u2010Cre viral vector was injected into the hippocampus of\n                      <jats:italic>Rptor<\/jats:italic>\n                      <jats:sup>flox\/flox<\/jats:sup>\n                      (regulatory\u2010associated protein of mTOR) mutant mice to inhibit mTOR activation in dentate gyrus granule cells. Four weeks after AAV\u2010Cre or AAV\u2010vehicle injection, mice underwent CCI injury and were subsequently assessed for mTOR pathway activation by Western blotting, neuronal death, and mossy fiber sprouting by immunopathological analysis, and posttraumatic seizures by video\u2010electroencephalographic monitoring.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AAV\u2010Cre injection primarily affected the dentate gyrus and inhibited hippocampal mTOR activation following CCI injury. AAV\u2010Cre\u2010injected mice had reduced neuronal death in dentate gyrus detected by Fluoro\u2010Jade B staining and decreased mossy fiber sprouting by ZnT3 immunostaining. Finally, AAV\u2010Cre\u2010injected mice exhibited a decrease in incidence of PTE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>mTOR pathway activation in dentate gyrus granule cells may at least partly mediate pathological abnormalities and epileptogenesis in models of TBI and PTE. Targeted modulation of mTOR activity in this hippocampal network may represent a focused therapeutic approach for antiepileptogenesis and prevention of PTE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18011","type":"journal-article","created":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T06:16:01Z","timestamp":1716012961000},"page":"2127-2137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A role of dentate gyrus mechanistic target of rapamycin activation in epileptogenesis in a mouse model of posttraumatic epilepsy"],"prefix":"10.1111","volume":"65","author":[{"given":"Dongjun","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurology and Hope Center for Neurological Disorders Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology and Hope Center for Neurological Disorders Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christin M.","family":"Godale","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas R.","family":"Rensing","sequence":"additional","affiliation":[{"name":"Department of Neurology and Hope Center for Neurological Disorders Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4405-2999","authenticated-orcid":false,"given":"Steve C.","family":"Danzer","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3796-743X","authenticated-orcid":false,"given":"Michael","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Neurology and Hope Center for Neurological Disorders Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-09926-w"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.44.s10.4.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1552923"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-014-0260-7"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16450"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2011.02.033"},{"issue":"8","key":"e_1_2_10_8_1","article-title":"Pharmacological treatments for preventing epilepsy following traumatic head injury","volume":"2015","author":"Thompson K","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.02005.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02341.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2014.00018"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01270.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31419-2"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21331"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0066-09.2009"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035885"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03513.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4852-10.2011"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064078"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2015.00163"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(07)63041-6"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270056"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20726"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03463.x"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.03.012"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.10.005"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb00875.x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111574"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31961-6"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.03.029"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0608-y"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42922-y"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1354-22.2022"},{"key":"e_1_2_10_34_1","doi-asserted-by":"crossref","unstructured":"CullenER SafariM MittelstadtI WestonMC.Hyperactivity of mTORC1 and mTORC2\u2010dependent signaling mediate epilepsy downstream of somatic PTEN loss.bioRxiv.2024.https:\/\/doi.org\/10.1101\/2023.08.18.553856","DOI":"10.7554\/eLife.91323.2"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.18011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T11:49:19Z","timestamp":1721130559000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.18011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,18]]},"references-count":33,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/epi.18011"],"URL":"https:\/\/doi.org\/10.1111\/epi.18011","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,18]]},"assertion":[{"value":"2024-01-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}