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Neuroinflammation is also present early in relevant brain regions during AD pathology progression. In addition, previous mechanistic studies in animal models link neuroinflammation as a contributor to neuropathology and cognitive impairment in traumatic brain injury (TBI) or AD-related models. Therefore, we explored the potential interplay of neuroinflammatory responses in TBI and AD by analysis of the temporal neuroinflammatory changes after TBI in an AD model, the APP\/PS1 knock-in (KI) mouse. Discrete temporal aspects of astrocyte, cytokine, and chemokine responses in the injured KI mice were delayed compared with the injured wild-type mice, with a peak neuroinflammatory response in the injured KI mice occurring at 7 d after injury. The neuroinflammatory responses were more persistent in the injured KI mice, leading to a chronic neuroinflammation. At late time points after injury, KI mice exhibited a significant impairment in radial arm water maze performance compared with sham KI mice or injured wild-type mice. Intervention with a small-molecule experimental therapeutic (MW151) that selectively attenuates proinflammatory cytokine production yielded improved cognitive behavior outcomes, consistent with a link between neuroinflammatory responses and altered risk for AD-associated pathology changes with head injury.<\/jats:p>","DOI":"10.1523\/jneurosci.0291-15.2015","type":"journal-article","created":{"date-parts":[[2015,4,22]],"date-time":"2015-04-22T16:29:41Z","timestamp":1429720181000},"page":"6554-6569","source":"Crossref","is-referenced-by-count":78,"title":["Closed Head Injury in an Age-Related Alzheimer Mouse Model Leads to an Altered Neuroinflammatory Response and Persistent Cognitive Impairment"],"prefix":"10.1523","volume":"35","author":[{"given":"Scott J.","family":"Webster","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda J.","family":"Van Eldik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7605-5866","authenticated-orcid":false,"given":"D. 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