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Anesthetized 11-day-old rats, neurologically equivalent to infants, were subjected to 1 impact\/day to the intact skull for 3 successive days. Repeated, but not single impact(s) resulted in spatial learning deficits (p\u2009&amp;lt;\u20090.05 compared to sham-injured animals) up to 5\u2009weeks postinjury. In the first week following single or repetitive brain injury, axonal and neuronal degeneration, and microglial activation were observed in the cortex, white matter, thalamus, and subiculum; the extent of the histopathologic damage was significantly greater in the repetitive-injured animals compared to single-injured animals. At 40\u2009days postinjury, loss of cortical, white matter and hippocampal tissue was evident only in the repetitive-injured animals, along with evidence of microglial activation in the white matter tracts and thalamus. Axonal injury and neurodegeneration were evident in the thalamus up to 40\u2009days postinjury in the repetitive-injured rats. These data demonstrate that while single closed head injury in the neonate rat is associated with pathologic alterations in the acute post-traumatic period, repetitive closed head injury results in sustained behavioral and pathologic deficits reminiscent of infants with abusive head trauma.<\/jats:p>","DOI":"10.1093\/jnen\/nlad048","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T22:23:36Z","timestamp":1688163816000},"page":"707-721","source":"Crossref","is-referenced-by-count":10,"title":["Repeated mild closed head injury in neonatal rats results in sustained cognitive deficits associated with chronic microglial activation and neurodegeneration"],"prefix":"10.1093","volume":"82","author":[{"given":"Ramesh","family":"Raghupathi","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine , Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupal","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine , Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine , Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy W","family":"Huh","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care, Children\u2019s Hospital of Philadelphia , Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"2024032523523818600_nlad048-B1","doi-asserted-by":"crossref","first-page":"e20200203","DOI":"10.1542\/peds.2020-0203","article-title":"Abusive head trauma in infants and children","volume":"145","author":"Narang","year":"2020","journal-title":"Pediatrics"},{"key":"2024032523523818600_nlad048-B2","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1056\/NEJM199806183382507","article-title":"Nonaccidental head injury in infants\u2014the \u201cshaken-baby syndrome\u201d","volume":"338","author":"Duhaime","year":"1998","journal-title":"N Engl J Med"},{"key":"2024032523523818600_nlad048-B3","doi-asserted-by":"crossref","first-page":"S157","DOI":"10.1016\/j.amepre.2007.12.021","article-title":"Using hospital discharge data to track inflicted traumatic brain injury","volume":"34","author":"Ellingson","year":"2008","journal-title":"Am J Prev Med"},{"key":"2024032523523818600_nlad048-B4","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1001\/jama.290.5.621","article-title":"A population-based study of inflicted traumatic brain injury in young children","volume":"290","author":"Keenan","year":"2003","journal-title":"JAMA"},{"key":"2024032523523818600_nlad048-B5","doi-asserted-by":"crossref","first-page":"e174","DOI":"10.1542\/peds.2004-2739","article-title":"Late neurologic and cognitive sequelae of inflicted traumatic brain injury in infancy","volume":"116","author":"Barlow","year":"2005","journal-title":"Pediatrics"},{"key":"2024032523523818600_nlad048-B6","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1159\/000121058","article-title":"Long-term outcome in infants with the shaking-impact syndrome","volume":"24","author":"Duhaime","year":"1996","journal-title":"Pediatr Neurosurg"},{"key":"2024032523523818600_nlad048-B7","first-page":"287","article-title":"Late intellectual and academic outcomes following traumatic brain injury sustained during early childhood","volume":"105","author":"Ewing-Cobbs","year":"2006","journal-title":"J Neurosurg"},{"key":"2024032523523818600_nlad048-B8","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/j.1469-8749.1995.tb11949.x","article-title":"Outcome and prognosis of whiplash shaken infant syndrome; 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