{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:35:24Z","timestamp":1790274924754,"version":"4.1.0"},"reference-count":67,"publisher":"SAGE Publications","issue":"7-8","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS135492"],"award-info":[{"award-number":["R01NS135492"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["K01HD097030"],"award-info":[{"award-number":["K01HD097030"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:p>\n                    Pediatric traumatic brain injury (TBI) triggers biological changes that may differ from those observed in non-brain injuries. Brain-derived neurotrophic factor (\n                    <jats:italic toggle=\"yes\">BDNF<\/jats:italic>\n                    ) DNA methylation (DNAm) may serve as a novel, dynamic biomarker of the brain\u2019s response and help identify TBI-specific epigenetic patterns relevant to later recovery. Therefore, the purpose of this study was to examine whether\n                    <jats:italic toggle=\"yes\">BDNF<\/jats:italic>\n                    DNAm differed between children with TBI and those with orthopedic injury (OI, comparison group) acutely and over time. Data were derived from the Epigenetic Effects on TBI Recovery study, a prospective, longitudinal cohort study conducted at UPMC Children\u2019s Hospital of Pittsburgh. Children aged 3\u201318 years hospitalized at a minimum of overnight for complicated mild-to-severe TBI or OI without head trauma were enrolled. Exclusion criteria included prior hospitalization for TBI, pre-existing neurological or psychiatric conditions, or sensory or motor impairments precluding study participation. Blood samples were collected during hospitalization (mean = 31.6 h post-injury) and at 6 (mean = 216.9 days) and 12 months (mean = 405.9 days) post-injury. The primary outcome variable was DNAm assessed via pyrosequencing at five quality-controlled CpG sites in the\n                    <jats:italic toggle=\"yes\">BDNF<\/jats:italic>\n                    gene (chromosome 11, Genome Reference Consortium Human Build 38 positions 27722033, 27722036, 27722047, 27701612, and 27701614). The primary exposure was injury type (TBI vs. OI), with severity (measured via Glasgow Coma Scale [GCS]) examined as a secondary exposure within the TBI group. Primary covariates included age, sex, and race; secondary covariates included pubertal status, age-adjusted body mass index, non-head injury severity, socioeconomic status, and psychosocial adversity. The final analysis sample included\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 189 participants with TBI and\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 105 participants with OI. Participants were 66.3% male, 83.2% White, and had a mean age of 10.6 (\u00b14.3) years at the time of enrollment. Acutely, children with TBI showed significantly lower DNAm at three of five sites (3.17\u20135.83% lower;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.0044 to 6.48E-06) while controlling for age, sex, and race. One site remained significantly lower at 12 months (8.56% lower;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.0045); no significant differences were observed at 6 months. Observed differences remained robust across sensitivity models adjusting for secondary covariates. GCS-measured TBI severity was not associated with DNAm at any time point. These findings suggest that\n                    <jats:italic toggle=\"yes\">BDNF<\/jats:italic>\n                    DNAm differs between children with TBI and those with OI, particularly in the acute period.\n                    <jats:italic toggle=\"yes\">BDNF<\/jats:italic>\n                    DNAm differences may reflect early biological responses that are specific to TBI.\n                  <\/jats:p>","DOI":"10.1177\/08977151251400737","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T15:18:35Z","timestamp":1765293515000},"page":"575-584","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Differential DNA Methylation of the Brain-Derived Neurotrophic Factor Gene is Observed after Pediatric Traumatic Brain Injury Compared with Orthopedic Injury"],"prefix":"10.1177","volume":"43","author":[{"given":"Lacey W.","family":"Heinsberg","sequence":"first","affiliation":[{"name":"Department of Health Promotion and Development, School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aboli","family":"Kesbhat","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Drexel University College of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailey","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Kaseman","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Stec","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nivinthiga","family":"Anton","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M.","family":"Kochanek","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith Owen","family":"Yeates","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Calgary, Calgary, Alberta, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Weeks","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Biostatistics and Health Data Science, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette P.","family":"Conley","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Development, School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Human Genetics, 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