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A key factor of TBI pathophysiology is neuroinflammation, which can involve the activation of the nucleotide\u2010binding domain leucine\u2010rich repeat protein 3 (NLRP3) inflammasome. Aberrant inflammation following injury has the ability to reduce the capacity to induce long\u2010term changes in synaptic plasticity, a leading mechanism for the development of learning and memory deficits following injury. This study investigated the potential of a novel NLRP3 inhibitor, AMS\u201017, to mitigate synaptic plasticity deficits following mild TBI (mTBI) in mice. Adult C57Bl\/6 mice were subjected to mTBI or a sham injury, and hippocampal slices were then prepared for field electrophysiological recordings in the medial perforant pathway of the dentate gyrus. We found that mTBI induced deficits in long\u2010term potentiation that were not immediate at 2\u2009h post\u2010injury but developed by 3\u2009days post\u2010injury. We next incubated slices in AMS\u201017 or a control solution prior to electrophysiological recordings. Here we found that incubation with AMS\u201017 rescued these LTP deficits, bringing them to levels observed in sham\u2010injured controls. Importantly, AMS\u201017 did not affect the capacity to induce LTP in sham\u2010injured mice. These findings suggest that targeting the NLRP3 inflammasome may offer a promising therapeutic strategy to reduce learning and memory impairments following mTBI. Further studies are needed to determine the optimal therapeutic window and long\u2010term efficacy of AMS\u201017 in mTBI.<\/jats:p>","DOI":"10.1002\/hipo.70072","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T02:54:39Z","timestamp":1768791279000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel\n                    <scp>NLRP3<\/scp>\n                    Inhibitor\n                    <scp>AMS<\/scp>\n                    \u201017 Rescues Deficits in Long\u2010Term Potentiation Following Mild Traumatic Brain Injury in Adult\n                    <scp>C57Bl<\/scp>\n                    \/6 Mice"],"prefix":"10.1002","volume":"36","author":[{"given":"Eric","family":"Eyolfson","sequence":"first","affiliation":[{"name":"School of Medical Sciences University of Victoria  Victoria Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Bettio","sequence":"additional","affiliation":[{"name":"School of Medical Sciences University of Victoria  Victoria Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Brand","sequence":"additional","affiliation":[{"name":"School of Medical Sciences University of Victoria  Victoria Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveen Kumar","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Texas at El Paso  El Paso Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Hamer","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Texas at El Paso  El Paso Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Salas","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Texas at El Paso  El Paso Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amol","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Texas at El Paso  El Paso Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6830-0160","authenticated-orcid":false,"given":"Brian R.","family":"Christie","sequence":"additional","affiliation":[{"name":"School of Medical Sciences University of Victoria  Victoria Canada"},{"name":"Department of Psychology San Diego State University  San Diego California USA"},{"name":"Island Medical Program and Department of Cellular and Physiological Sciences University of British Columbia  Victoria Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.07.028"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2007.0451"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2008.04.038"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.75"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-0925"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/2398212820979802"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1910-21.2022"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00862-y"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2021.12.006"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2019.6656"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.22142"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20151"},{"key":"e_1_2_10_14_1","first-page":"e64592","article-title":"Assessing Changes in Synaptic Plasticity Using an Awake Closed\u2010Head Injury Model of Mild Traumatic Brain Injury","volume":"191","author":"Christie B. 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