{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:41:05Z","timestamp":1786495265108,"version":"build-2736575974"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS098740"],"award-info":[{"award-number":["NS098740"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cognitive losses resulting from severe brain trauma have long been associated with the focal region of tissue damage, leading to devastating functional impairment. For decades, researchers have focused on the sequelae of cellular alterations that exist within the perilesional tissues; however, few pharmacological therapies are available to patients.<\/jats:p>\n                  <jats:p>To examine whether expansive global synaptic damage underlies cognitive losses associated with brain injury, we evaluated the influence of D-serine on synaptic damage in male and female wild-type mice as well as mice deficient in microglial serine racemase (TMEM119creErt2:SRRfl\/fl) or neuronal GluN2B (CamKIIcreErt2:Grin2bfl\/fl). We measured biochemical alterations in synaptic proteins, dendritic spine numbers and morphology, electrophysiological responses, and learning and memory behaviour. Single-cell analysis was employed to examine cell-type specific contributions, and perilesional tissues from 41 traumatic brain injury (TBI) patients were analysed for mRNA and\/or protein differences.<\/jats:p>\n                  <jats:p>Our findings demonstrate that synaptic damage results from the prolonged increase in D-serine release from activated microglia and astrocytes, which leads to hyperactivation of perisynaptic N-methyl-D-aspartate receptors and tagging of damaged synapses by complement components. We show that this mechanistic pathway for synaptic pruning is reversible at several stages within the acute period of brain injury, and that these key factors are also present in human brain injury.<\/jats:p>\n                  <jats:p>We conclude that prolonged glial D-serine release after brain injury leads to the reactivation of developmental pruning processes that underlie synaptic losses. Targeting specific molecules in this pathway may represent a new therapeutic strategy for protecting TBI patients from cognitive dysfunction.<\/jats:p>","DOI":"10.1093\/brain\/awaf293","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T11:38:53Z","timestamp":1754998733000},"page":"918-933","source":"Crossref","is-referenced-by-count":6,"title":["Cognitive loss after brain trauma results from sex-specific activation of synaptic pruning processes"],"prefix":"10.1093","volume":"149","author":[{"given":"Dena","family":"Arizanovska","sequence":"first","affiliation":[{"name":"The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald F","family":"Bush","sequence":"additional","affiliation":[{"name":"The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A","family":"Dallera","sequence":"additional","affiliation":[{"name":"The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwarotimi O","family":"Folorunso","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]},{"name":"Translational Psychiatry Laboratory, McLean Hospital , Belmont, MA 02478 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer B","family":"Frye","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, University of Arizona , Tucson, AZ 85721 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian P","family":"Doyle","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, University of Arizona , Tucson, AZ 85721 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R","family":"Jagid","sequence":"additional","affiliation":[{"name":"The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Wolosker","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Rappaport Faculty of Medicine, Technion\u2013Israel Institute of Technology , Haifa 31096 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo A","family":"Monaco","sequence":"additional","affiliation":[{"name":"The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joacir","family":"Graciolli Cordeiro","sequence":"additional","affiliation":[{"name":"The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coleen M","family":"Atkins","sequence":"additional","affiliation":[{"name":"The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Griswold","sequence":"additional","affiliation":[{"name":"The John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2680-1220","authenticated-orcid":false,"given":"Daniel J","family":"Liebl","sequence":"additional","affiliation":[{"name":"The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"2026030512073474000_awaf293-B1","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.3171\/2017.10.JNS17352","article-title":"Estimating the global incidence of traumatic brain injury","volume":"130","author":"Dewan","year":"2019","journal-title":"J 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