{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:49:30Z","timestamp":1787014170626,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T00:00:00Z","timestamp":1631923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002736","name":"Citizens United for Research in Epilepsy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002736","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Effective treatment for the prevention of posttraumatic epilepsy is still not available. Here, we sought to determine whether blocking receptor for advanced glycation end products (RAGE) or toll\u2010like receptor 4 (TLR4) signaling pathways would prevent posttraumatic epileptogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a mouse undercut model of posttraumatic epilepsy, daily injections of saline, RAGE monoclonal antibody (mAb), or TAK242, a TLR4 inhibitor, were made for 1\u00a0week. Their effects on seizure susceptibility and spontaneous epileptic seizures were evaluated with a pentylenetetrazol (PTZ) test in 2\u00a0weeks and with continuous video and wireless electroencephalography (EEG) monitoring between 2 and 6\u00a0weeks after injury, respectively. Seizure susceptibility after undercut in RAGE knockout mice was also evaluated with the PTZ test. The lesioned cortex was analyzed with immunohistology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Undercut animals treated with RAGE mAb or TAK242\u00a0showed significantly higher seizure threshold than saline\u2010treated undercut mice. Consistently, undercut injury in RAGE knockout mice did not cause a reduction in seizure threshold in the PTZ test. EEG and video recordings revealed a significant decrease in the cumulative spontaneous seizure events in the RAGE mAb\u2010 or TAK242\u2010treated group (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001, when the RAGE mAb or TAK242\u00a0group is compared with the saline group). The lesioned cortical tissues of RAGE mAb\u2010 or TAK242\u2010treated undercut group showed higher neuronal densities of Nissl staining and higher densities of glutamic acid decarboxylase 67\u2010immunoreactive interneurons than the saline\u2010treated undercut group. Immunostaining to GFAP and Iba\u20101 revealed lower densities of astrocytes and microglia in the cortex of the treatment groups, suggesting reduced glia activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>RAGE and TLR4\u00a0signaling are critically involved in posttraumatic epileptogenesis. Blocking these pathways early after traumatic brain injury is a promising strategy for preventing posttraumatic epilepsy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.17069","type":"journal-article","created":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T03:04:03Z","timestamp":1631934243000},"page":"3105-3116","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Blocking receptor for advanced glycation end products (RAGE) or toll\u2010like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8233-9961","authenticated-orcid":false,"given":"Xingjie","family":"Ping","sequence":"first","affiliation":[{"name":"Department of Anatomy, Cell Biology and Physiology Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Spinal Cord and Brain Injury Research Group Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Chai","sequence":"additional","affiliation":[{"name":"Neurobiology Research Center Shanxi Key Laboratory of Innovative Drugs for Serious Illness College of Basic Medicine Shanxi University of Chinese Medicine Jinzhong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Affiliated Hangzhou First People's Hospital Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cungen","family":"Ma","sequence":"additional","affiliation":[{"name":"Neurobiology Research Center Shanxi Key Laboratory of Innovative Drugs for Serious Illness College of Basic Medicine Shanxi University of Chinese Medicine Jinzhong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fletcher A","family":"White","sequence":"additional","affiliation":[{"name":"Spinal Cord and Brain Injury Research Group Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Anesthesia Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Research and Development Services Richard L. 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