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Post-natal day (PND) 18 rats were subjected to either one, two, or three mild TBIs (mTBI) or an equivalent number of sham insults 24\u2009h apart. After one or two mTBIs or sham insults, histology was evaluated at 7 days. After three mTBIs or sham insults, motor (d1\u20135), cognitive (d11\u201392), and histological (d21\u201392) outcome was evaluated. At 7 days, silver degeneration staining revealed axonal argyrophilia in the external capsule and corpus callosum after a single mTBI, with a second impact increasing axonal injury. Iba-1 immunohistochemistry showed amoeboid shaped microglia within the amygdalae bilaterally after mTBI. After three mTBI, there were no differences in beam balance, Morris water maze, and elevated plus maze performance versus sham. The rmTBI rats, however, showed impairment in novel object recognition and fear conditioning. Axonal silver staining was observed only in the external capsule on d21. Iba-1 staining did not reveal activated microglia on d21 or d92. In conclusion, mTBI results in traumatic axonal injury and microglial activation in the immature brain with repeated impact exacerbating axonal injury. The rmTBI in the immature brain leads to long-term associative learning deficit in adulthood. Defining the mechanisms damage from rmTBI in the developing brain could be vital for identification of therapies for children.<\/jats:p>","DOI":"10.1089\/neu.2015.3958","type":"journal-article","created":{"date-parts":[[2015,7,27]],"date-time":"2015-07-27T12:43:03Z","timestamp":1438000983000},"page":"641-651","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":69,"title":["Repetitive Mild Traumatic Brain Injury in the Developing Brain: Effects on Long-Term Functional Outcome and Neuropathology"],"prefix":"10.1177","volume":"33","author":[{"given":"Emin","family":"Fidan","sequence":"first","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Lewis","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony E.","family":"Kline","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"},{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Garman","sequence":"additional","affiliation":[{"name":"Consultants in Veterinary Pathology, Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Alexander","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey P.","family":"Cheng","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"},{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina O.","family":"Bondi","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"},{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.B.","family":"Clark","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"},{"name":"Children's Hospital of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Dezfulian","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"},{"name":"Children's Hospital of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M.","family":"Kochanek","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"},{"name":"Children's Hospital of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerian E.","family":"Kagan","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00fclya","family":"Bay\u0131r","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"},{"name":"University of Pittsburgh"},{"name":"Children's Hospital of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,4,1]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"Faul M. 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