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The sterile alpha and TIR motif containing 1 (SARM1) protein has been identified to play a key role in neurodegeneration and inflammatory cascades. Therefore, we hypothesized that the inhibition of SARM1 would prevent glial reactivity following TBI and could be targeted for therapeutic intervention. TBI was modeled in wild type (WT) and SARM1 knock\u2010out (SARM1\u2010KO) mice of both biological sexes by midline fluid percussion injury. At 7 or 28\u2009days post\u2010injury, brains were collected to examine glial reactivity via immunohistochemistry and compared to na\u00efve controls. The density of microglia and glial fibrillary acidic protein (GFAP) immunoreactivity of astrocytes was significantly increased across time post\u2010injury. Furthermore, microglial morphological changes and increased colocalization with a surrogate marker of phagocytosis (CD68) were evident at 7\u2009days post\u2010injury. In the absence of SARM1, microglial density and colocalization with CD68 was greater compared with WT animals, regardless of TBI. However, there were no differences in GFAP immunoreactivity with the genetic deletion of SARM1. When investigating biological sexes, the TBI\u2010induced increase in microglial density and cell volume was greater in male mice at 7\u2009days post\u2010injury; however, microglia were more deramified in females. There were no significant differences in GFAP immunoreactivity between male and female mice. These results indicate that the genetic deletion of SARM1 is not sufficient to alter GFAP\u2010labeling of astrocytes; however, SARM1 appears to impact microglial density and CD68 colocalization in the na\u00efve and injured brain.<\/jats:p>","DOI":"10.1002\/glia.70095","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T11:55:55Z","timestamp":1761134155000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Independent Effects of Biological Sex and\n                    <scp>SARM1<\/scp>\n                    Deletion on Glia Following Diffuse Traumatic Brain Injury"],"prefix":"10.1002","volume":"74","author":[{"given":"Yasmine V.","family":"Doust","sequence":"first","affiliation":[{"name":"Wicking Dementia Research and Education Centre, Health University of Tasmania  Hobart Tasmania Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel K.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology University of Colorado Boulder  Boulder Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross C.","family":"Langley","sequence":"additional","affiliation":[{"name":"Wicking Dementia Research and Education Centre, Health University of Tasmania  Hobart Tasmania Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna E.","family":"King","sequence":"additional","affiliation":[{"name":"Wicking Dementia Research and Education Centre, Health University of Tasmania  Hobart Tasmania Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2497-4347","authenticated-orcid":false,"given":"Jenna M.","family":"Ziebell","sequence":"additional","affiliation":[{"name":"Wicking Dementia Research and Education Centre, Health University of Tasmania  Hobart Tasmania Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-015-0228-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3648"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22867"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2011.1923"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2022.0416"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx180"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v067.i01"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/neur.2020.0046"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01193-8"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.32614\/RJ-2017-066"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709002105"},{"key":"e_1_2_10_14_1","volume-title":"Model Selection and Multimodal Inference; 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