{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:24:16Z","timestamp":1789662256005,"version":"4.0.1"},"reference-count":66,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG057525"],"award-info":[{"award-number":["R01AG057525"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32GM135134"],"award-info":[{"award-number":["T32GM135134"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Systemic perturbations can drive a neuroimmune cascade after surgical trauma, including affecting the blood\u2013brain barrier (BBB), activating microglia, and contributing to cognitive deficits such as delirium. Delirium superimposed on dementia (DSD) is a particularly debilitating complication that renders the brain further vulnerable to neuroinflammation and neurodegeneration, albeit these molecular mechanisms remain poorly understood. Here, we have used an orthopedic model of tibial fracture\/fixation in APPSwDI\/mNos2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    AD (CVN\u2010AD) mice to investigate relevant pathogenetic mechanisms underlying DSD. We conducted the present study in 6\u2010month\u2010old CVN\u2010AD mice, an age at which we speculated amyloid\u2010\u03b2 pathology had not saturated BBB and neuroimmune functioning. We found that URMC\u2010099, our brain\u2010penetrant anti\u2010inflammatory neuroprotective drug, prevented inflammatory endothelial activation, breakdown of the BBB, synapse loss, and microglial activation in our DSD model. Taken together, our data link post\u2010surgical endothelial activation, microglial MafB immunoreactivity, and synapse loss as key substrates for DSD, all of which can be prevented by URMC\u2010099.\n                  <\/jats:p>","DOI":"10.1096\/fj.202200184rr","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T05:00:01Z","timestamp":1652158801000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["URMC\u2010099 prophylaxis prevents hippocampal vascular vulnerability and synaptic damage in an orthopedic model of delirium superimposed on dementia"],"prefix":"10.1096","volume":"36","author":[{"given":"Patrick","family":"Miller\u2010Rhodes","sequence":"first","affiliation":[{"name":"Center for Neurotherapeutics Discovery, Department of Neurology University of Rochester Medical Center  Rochester New York USA"},{"name":"Neuroscience Graduate Program University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Neurotherapeutics Discovery, Department of Neurology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravikanth","family":"Velagapudi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Center for Translational Pain Medicine Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1803-5853","authenticated-orcid":false,"given":"Niccol\u00f2","family":"Terrando","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Center for Translational Pain Medicine Duke University Medical Center  Durham North Carolina USA"},{"name":"Department of Cell Biology Duke University Medical Center  Durham North Carolina USA"},{"name":"Department of Immunology Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harris A.","family":"Gelbard","sequence":"additional","affiliation":[{"name":"Center for Neurotherapeutics Discovery, Department of Neurology University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Neurology University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Neuroscience University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Pediatrics University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Microbiology &amp; Immunology University of Rochester Medical Center  Rochester New York 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