{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:52:05Z","timestamp":1790196725389,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chilean Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","award":["11190882"],"award-info":[{"award-number":["11190882"]}]},{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["21201129"],"award-info":[{"award-number":["21201129"]}],"id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Postoperative delirium (POD), an acute cognitive dysfunction linked to morbidity and mortality, is characterized by memory impairments and disturbances in consciousness, particularly in patients aged 65 and older. Neuroinflammation and NAD+ imbalance are key mechanisms behind POD, leading to synaptic and cognitive deterioration. However, how surgery contributes to POD and neuroinflammation remains unclear, and effective treatments are lacking. Here we used a rodent model of bone fracture to examine the impact of surgery on synaptic plasticity, inflammation, and cognition. Additionally, we explored whether treatment with nicotinamide (NAM), a NAD+ precursor, reduced the neuroinflammation and metabolic imbalance caused by surgery. Female C57BL\/6J mice aged 20\u201322 months underwent tibial fracture surgery and received pre- and post-surgery NAM treatment. Neuroinflammation, synaptic plasticity, and cognition were assessed 72 hours post-surgery via long-term potentiation (LTP) assays, dendritic spine counting, and behavioral tests (open field maze and Y-maze). Tibial fracture surgery decreased LTP, dendritic spine density, and hippocampal-dependent memory function, and increased hippocampal inflammatory markers (IL-1\u03b2 mRNA, CD38, and SIRT1 protein content); NAM pretreatment prevented these changes. Given surgery\u2019s adverse effects on LTP and dendritic spine density, we assessed cellular oxidative state and brain-derived neurotrophic factor (BDNF) protein levels. We found that surgery increased the oxidation of ryanodine receptor calcium channels (cellular redox sensors), and decreased BDNF protein levels; NAM supplementation mitigated both effects and prevented the cognitive decline and synaptic plasticity deficits while reducing inflammation post-surgery by lowering IL-1\u03b2 and CD38 protein levels. We propose that the CD38 signaling pathway mediates these NAM protective effects.<\/jats:p>","DOI":"10.1093\/gerona\/glae303","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T13:18:01Z","timestamp":1737119881000},"source":"Crossref","is-referenced-by-count":6,"title":["Nicotinamide Prevents the Plasticity Impairments and the Cognitive Dysfunction Caused by Bone Fracture in Older Mice"],"prefix":"10.1093","volume":"80","author":[{"given":"Tatiana","family":"Guncay","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Cl\u00ednico Universidad de Chile , Santiago ,","place":["Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Concha","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Cl\u00ednico Universidad de Chile , Santiago ,","place":["Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Lobos","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Cl\u00ednico Universidad de Chile , Santiago ,","place":["Chile"]},{"name":"Clinical and Molecular Pharmacology Program, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile , Santiago ,","place":["Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamileth","family":"More","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Cl\u00ednico Universidad de Chile , Santiago ,","place":["Chile"]},{"name":"Laboratory of Translational Psychiatry, Department of Neuroscience and Department de Psychiatry North, Universidad de Chile , Santiago 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Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Cl\u00ednico Universidad de Chile , Santiago ,","place":["Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Bra\u00f1ez","sequence":"additional","affiliation":[{"name":"Servicio de Traumatolog\u00eda, Hospital San Jos\u00e9 , Santiago ,","place":["Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Quiroz","sequence":"additional","affiliation":[{"name":"Geroscience Center for Brain Health and Metabolism (GERO) , Santiago ,","place":["Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genaro","family":"Barrientos","sequence":"additional","affiliation":[{"name":"Physiology and Biophysics Program, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile , Santiago ,","place":["Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"Physiology and Biophysics Program, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile , Santiago ,","place":["Chile"]},{"name":"Center for Exercise, Metabolism and Cancer Studies, Faculty of Medicine, Universidad de Chile , Santiago ,","place":["Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Salech","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Cl\u00ednico Universidad de Chile , Santiago ,","place":["Chile"]},{"name":"Geroscience Center for Brain Health and Metabolism (GERO) , Santiago 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