{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T20:10:44Z","timestamp":1772827844491,"version":"3.50.1"},"reference-count":80,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,26]]},"abstract":"\n OBJECTIVE<\/jats:title>\n Traumatic brain injury (TBI) is a leading cause of acquired neurological disability in children of both sexes. Therapies that improve neurological disability in animal TBI models have universally failed in humans. Successful transition to clinical application should increase if experimental TBI models use animals that are more similar to humans and collect clinically relevant biomarkers. Porcine models of human disease are strong predictors of clinical efficacy. However, studies using immature swine of both sexes and serial collection of biological samples after TBI are lacking. In the authors\u2019 rat model of pediatric TBI, docosahexaenoic acid (DHA) improved outcomes and decreased white matter injury, neuroinflammation, and oxidative stress. The authors conducted a proof-of-concept study to evaluate the feasibility of obtaining serial blood, cerebrospinal fluid (CSF), and urine samples from piglets of both sexes after TBI using fluid percussion injury (FPI), and to assess the utility of these samples for measuring clinically relevant biomarkers in a preclinical pediatric TBI model.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n After pilot testing of a CSF reservoir in cadaver piglets, the authors conducted FPI followed by reservoir placement in live 4-week-old male and female piglets.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n The authors succeeded in obtaining all 3 types of samples and measuring biomarkers of white matter injury, neuroinflammation, and oxidative stress. When inserted to an optimal depth of 10 mm, CSF reservoir function was preserved for 3\u20137 days despite normal piglet activity. Surgery-related mortality (occurring within 1 hour) was 3\/36 piglets. One piglet had a quickly resolved scalp infection. FPI increased serum neurofilament light (NfL), a marker of axonal injury, at postinjury day (PID) 1 and 7 in males, blunted by DHA, although the sample size was small. At PID 3, FPI increased CSF interleukin (IL)\u20134, -8, -12, and -18. DHA abrogated the FPI-induced increase in IL-8 in males. FPI increased IL-12 in DHA-treated females but not control (coconut oil\u2013treated) females. Female sex was associated with increased levels of 10 of the 13 CSF cytokines even in the absence of FPI. At PID 1, the authors observed markedly decreased CSF total antioxidant capacity, a measure of oxidative stress, in all groups.<\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n Modified piglet FPI allowed serial collection of CSF, urine, and blood samples during the 1st week after surgery. The authors anticipate that this model will be useful for preclinical pharmacokinetic and efficacy studies that require longer term survival and serial biofluid collection after TBI.<\/jats:p>\n <\/jats:sec>","DOI":"10.3171\/2025.6.peds2555","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T03:21:10Z","timestamp":1758943270000},"page":"738-746","source":"Crossref","is-referenced-by-count":2,"title":["Effects of sex, injury, and docosahexaenoic acid in a preclinical porcine model of pediatric traumatic brain injury using novel serial collection of CSF, urine, and serum biomarkers"],"prefix":"10.3171","volume":"36","author":[{"given":"Michelle E.","family":"Schober","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Critical Care, University of Utah, Salt Lake City, Utah;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia R.","family":"Terry","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Critical Care, University of Utah, Salt Lake City, Utah;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin C.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Critical Care, University of Utah, Salt Lake City, Utah;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noah","family":"Slusher","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Critical Care, University of Utah, Salt Lake City, Utah;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James Patterson","family":"McAllister","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Gensel","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Kentucky College of Medicine, Lexington;"},{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, Kentucky; and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"issue":"4","key":"b1","series-title":"Am J Prev Med","first-page":"754","article-title":"Global burden of traumatic brain injury in 204 countries and territories from 1990 to 2021","volume":"68","author":"Zhong H","year":"2025","unstructured":"Zhong H, Feng Y, Shen J, Global burden of traumatic brain injury in 204 countries and territories from 1990 to 2021. Am J Prev Med. 2025;68(4):754\u2013763."},{"issue":"9","key":"b2","series-title":"Children (Basel)","first-page":"1","article-title":"Burden of traumatic brain injuries in children and adolescents in Europe: hospital discharges, deaths and years of life lost","volume":"2022","author":"Majdan M","unstructured":"Majdan M, Melichova J, Plancikova D, Burden of traumatic brain injuries in children and adolescents in Europe: hospital discharges, deaths and years of life lost. Children (Basel). 2022;(9):1."},{"issue":"11","key":"b3","series-title":"Am J Public Health","first-page":"2074","article-title":"Incidence of disability among children 12 months after traumatic brain injury","volume":"102","author":"Rivara FP","year":"2012","unstructured":"Rivara FP, Koepsell TD, Wang J, Incidence of disability among children 12 months after traumatic brain injury. Am J Public Health. 2012;102(11):2074\u20132079."},{"issue":"1 Pt 2","key":"b4","series-title":"Am J Physiol","first-page":"R135","article-title":"Eicosanoids in third ventricular cerebrospinal fluid of fetal and newborn sheep","volume":"264","author":"Jones SA","year":"1993","unstructured":"Jones SA, Adamson SL, Bishai I, Lees J, Engelberts D, Coceani F. Eicosanoids in third ventricular cerebrospinal fluid of fetal and newborn sheep. Am J Physiol. 1993;264(1 Pt 2):R135-R142."},{"key":"b5","series-title":"Sci Transl Med","first-page":"eabd5758","article-title":"Importance of the pig as a human biomedical model","volume":"13(621)","author":"Lunney JK","year":"2021","unstructured":"Lunney JK, Van Goor A, Walker KE, Hailstock T, Franklin J, Dai C. Importance of the pig as a human biomedical model. Sci Transl Med. 2021;13(621):eabd5758."},{"issue":"3","key":"b6","series-title":"Neural Regen Res","first-page":"413","article-title":"The pig as a preclinical traumatic brain injury model: current models, functional outcome measures, and translational detection strategies","volume":"14","author":"Kinder HA","year":"2019","unstructured":"Kinder HA, Baker EW, West FD. The pig as a preclinical traumatic brain injury model: current models, functional outcome measures, and translational detection strategies. Neural Regen Res. 2019;14(3):413-424."},{"issue":"4","key":"b7","series-title":"Dev Neurosci","first-page":"291","article-title":"Brain growth of the domestic pig (Sus scrofa) from 2 to 24 weeks of age: a longitudinal MRI study","volume":"34","author":"Conrad MS","year":"2012","unstructured":"Conrad MS, Dilger RN, Johnson RW. Brain growth of the domestic pig (Sus scrofa) from 2 to 24 weeks of age: a longitudinal MRI study. Dev Neurosci. 2012;34(4):291-298."},{"issue":"21-22","key":"b8","series-title":"J Neurotrauma","first-page":"2270","article-title":"Pediatric moderate and severe traumatic brain injury: a systematic review of clinical practice guideline recommendations","volume":"40","author":"Ben Abdeljelil A","year":"2023","unstructured":"Ben Abdeljelil A, Freire GC, Yanchar N, Pediatric moderate and severe traumatic brain injury: a systematic review of clinical practice guideline recommendations. J Neurotrauma. 2023;40(21-22):2270-2281."},{"issue":"10","key":"b9","series-title":"Childs Nerv Syst","first-page":"1693","article-title":"Pre-clinical models in pediatric traumatic brain injury-challenges and lessons learned","volume":"33","author":"Kochanek PM","year":"2017","unstructured":"Kochanek PM, Wallisch JS, Bay\u0131r H, Clark RSB. Pre-clinical models in pediatric traumatic brain injury-challenges and lessons learned. Childs Nerv Syst. 2017;33(10):1693-1701."},{"key":"b10","series-title":"J Neuroinflammation","first-page":"40","article-title":"Disruption of Midkine gene reduces traumatic brain injury through the modulation of neuroinflammation","volume":"17(1)","author":"Takada S","year":"2020","unstructured":"Takada S, Sakakima H, Matsuyama T, Disruption of Midkine gene reduces traumatic brain injury through the modulation of neuroinflammation. J Neuroinflammation. 2020;17(1):40."},{"issue":"4","key":"b11","series-title":"Pediatr Neurol","first-page":"227","article-title":"Selective vulnerability in the developing central nervous system","volume":"30","author":"McQuillen PS","year":"2004","unstructured":"McQuillen PS, Ferriero DM. Selective vulnerability in the developing central nervous system. Pediatr Neurol. 2004;30(4):227\u2013235."},{"issue":"5","key":"b12","series-title":"J Agric Food Chem","first-page":"1647","article-title":"Antioxidant activity of docosahexaenoic acid (DHA) and its regulatory roles in mitochondria","volume":"69","author":"Li G","year":"2021","unstructured":"Li G, Li Y, Xiao B, Antioxidant activity of docosahexaenoic acid (DHA) and its regulatory roles in mitochondria. J Agric Food Chem. 2021;69(5):1647\u20131655."},{"issue":"3","key":"b13","series-title":"J Neurosci Res","first-page":"575","article-title":"Docosahexaenoic acid modulates inflammatory and antineurogenic functions of activated microglial cells","volume":"90","author":"Antonietta Ajmone-Cat M","year":"2012","unstructured":"Antonietta Ajmone-Cat M, Lavinia Salvatori M, De Simone R, Docosahexaenoic acid modulates inflammatory and antineurogenic functions of activated microglial cells. J Neurosci Res. 2012;90(3):575-587."},{"issue":"4","key":"b14","series-title":"J Neurotrauma","first-page":"390","article-title":"Dietary docosahexaenoic acid improves cognitive function, tissue sparing, and magnetic resonance imaging indices of edema and white matter injury in the immature rat after traumatic brain injury","volume":"33","author":"Schober ME","year":"2016","unstructured":"Schober ME, Requena DF, Abdullah OM, Dietary docosahexaenoic acid improves cognitive function, tissue sparing, and magnetic resonance imaging indices of edema and white matter injury in the immature rat after traumatic brain injury. J Neurotrauma. 2016;33(4):390-402."},{"key":"b15","series-title":"Exp Neurol","first-page":"112971","article-title":"Docosahexaenoic acid decreased neuroinflammation in rat pups after controlled cortical impact","volume":"320","author":"Schober ME","year":"2019","unstructured":"Schober ME, Requena DF, Casper TC, Docosahexaenoic acid decreased neuroinflammation in rat pups after controlled cortical impact. Exp Neurol. 2019;320:112971."},{"issue":"1","key":"b16","series-title":"Fluids Barriers CNS","first-page":"49","article-title":"A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments","volume":"18","author":"McAllister JP","year":"2021","unstructured":"McAllister JP, Talcott MR, Isaacs AM, A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments. Fluids Barriers CNS. 2021;18(1):49."},{"issue":"1-2","key":"b17","series-title":"Brain Res Bull","first-page":"1","article-title":"Stereotaxic atlas of the pig brain","volume":"49","author":"F\u00e9lix B","year":"1999","unstructured":"F\u00e9lix B, L\u00e9ger ME, Albe-Fessard D, Marcilloux JC, Rampin O, Laplace JP. Stereotaxic atlas of the pig brain. Brain Res Bull. 1999;49(1-2):1\u2013137."},{"issue":"1","key":"b18","series-title":"Int J Dev Neurosci","first-page":"31","article-title":"Effects of lateral fluid percussion injury on cholinergic markers in the newborn piglet brain","volume":"28","author":"Donat CK","year":"2010","unstructured":"Donat CK, Walter B, Kayser T, Effects of lateral fluid percussion injury on cholinergic markers in the newborn piglet brain. Int J Dev Neurosci. 2010;28(1):31-38."},{"issue":"8","key":"b19","series-title":"J Neurotrauma","first-page":"1076","article-title":"Age-dependent effects of severe traumatic brain injury on cerebral dopaminergic activity in newborn and juvenile pigs","volume":"21","author":"Walter B","year":"2004","unstructured":"Walter B, Brust P, F\u00fcchtner F, Age-dependent effects of severe traumatic brain injury on cerebral dopaminergic activity in newborn and juvenile pigs. J Neurotrauma. 2004;21(8):1076\u20131089."},{"issue":"1","key":"b20","series-title":"Sci Rep","first-page":"15907","article-title":"Early weaning and biological sex shape long-term immune and metabolic responses in pigs","volume":"13","author":"Fardisi M","year":"2023","unstructured":"Fardisi M, Thelen K, Groenendal A, Early weaning and biological sex shape long-term immune and metabolic responses in pigs. Sci Rep. 2023;13(1):15907."},{"issue":"2","key":"b21","series-title":"J Reprod Fertil","first-page":"377","article-title":"Changes in serum testosterone concentrations in the male pig during development","volume":"53","author":"Colenbrander B","year":"1978","unstructured":"Colenbrander B, de Jong FH, Wensing CJ. Changes in serum testosterone concentrations in the male pig during development. J Reprod Fertil. 1978;53(2):377\u2013380."},{"issue":"3","key":"b22","series-title":"J Neurotrauma","first-page":"359","article-title":"Craniotomy: true sham for traumatic brain injury, or a sham of a sham?","volume":"28","author":"Cole JT","year":"2011","unstructured":"Cole JT, Yarnell A, Kean WS, Craniotomy: true sham for traumatic brain injury, or a sham of a sham?. J Neurotrauma. 2011;28(3):359\u2013369."},{"issue":"2","key":"b23","series-title":"Can J Anim Sci","first-page":"457","article-title":"An efficient method for collecting urine from neonatal pigs","volume":"59","author":"Parker RO","year":"1979","unstructured":"Parker RO, Williams PEV, Aherne FX, Young BA. An efficient method for collecting urine from neonatal pigs. Can J Anim Sci. 1979;59(2):457\u2013458."},{"issue":"6","key":"b24","series-title":"Med Sci Sports Exerc","first-page":"974","article-title":"Effect of docosahexaenoic acid on a biomarker of head trauma in American football","volume":"48","author":"Oliver JM","year":"2016","unstructured":"Oliver JM, Jones MT, Kirk KM, Effect of docosahexaenoic acid on a biomarker of head trauma in American football. Med Sci Sports Exerc. 2016;48(6):974-982."},{"issue":"2-3","key":"b25","series-title":"Prostaglandins Leukot Essent Fatty Acids","first-page":"125","article-title":"Toxicology and safety of DHA","volume":"81","author":"Lien EL","year":"2009","unstructured":"Lien EL. Toxicology and safety of DHA. Prostaglandins Leukot Essent Fatty Acids. 2009;81(2-3):125-132."},{"issue":"10","key":"b26","series-title":"J Neurotrauma","first-page":"1185","article-title":"Valproic acid treatment decreases serum glial fibrillary acidic protein and neurofilament light chain levels in swine subjected to traumatic brain injury","volume":"35","author":"Korley FK","year":"2018","unstructured":"Korley FK, Nikolian VC, Williams AM, Dennahy IS, Weykamp M, Alam HB. Valproic acid treatment decreases serum glial fibrillary acidic protein and neurofilament light chain levels in swine subjected to traumatic brain injury. J Neurotrauma. 2018;35(10):1185-1191."},{"issue":"9","key":"b27","series-title":"Lancet Neurol","first-page":"782","article-title":"Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study","volume":"17","author":"Bazarian JJ","year":"2018","unstructured":"Bazarian JJ, Biberthaler P, Welch RD, Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018;17(9):782\u2013789."},{"key":"b28","series-title":"EBioMedicine","first-page":"102785","article-title":"Blood biomarkers on admission in acute traumatic brain injury: relations to severity, CT findings and care path in the CENTER-TBI study","volume":"56","author":"Czeiter E","year":"2020","unstructured":"Czeiter E, Amrein K, Gravesteijn BY, Blood biomarkers on admission in acute traumatic brain injury: relations to severity, CT findings and care path in the CENTER-TBI study. EBioMedicine. 2020;56:102785."},{"issue":"1","key":"b29","series-title":"Pediatr Crit Care Med","first-page":"4","article-title":"Biochemical, cellular, and molecular mechanisms in the evolution of secondary damage after severe traumatic brain injury in infants and children: lessons learned from the bedside","volume":"1","author":"Kochanek PM","year":"2000","unstructured":"Kochanek PM, Clark RSB, Ruppel RA, Biochemical, cellular, and molecular mechanisms in the evolution of secondary damage after severe traumatic brain injury in infants and children: lessons learned from the bedside. Pediatr Crit Care Med. 2000;1(1):4\u201319."},{"issue":"15-16","key":"b30","series-title":"J Neurotrauma","first-page":"1914","article-title":"Distinct serum glial fibrillary acidic protein and neurofilament light time-courses after rapid head rotations","volume":"41","author":"Huber CM","year":"2024","unstructured":"Huber CM, Thakore AD, Oeur RA, Margulies SS. Distinct serum glial fibrillary acidic protein and neurofilament light time-courses after rapid head rotations. J Neurotrauma. 2024;41(15-16):1914-1928."},{"issue":"2","key":"b31","series-title":"J Perinat Med","first-page":"209","article-title":"DHA reduces oxidative stress following hypoxia-ischemia in newborn piglets: a study of lipid peroxidation products in urine and plasma","volume":"46","author":"Huun MU","year":"2018","unstructured":"Huun MU, Garberg HT, Escobar J, DHA reduces oxidative stress following hypoxia-ischemia in newborn piglets: a study of lipid peroxidation products in urine and plasma. J Perinat Med. 2018;46(2):209-217."},{"issue":"5","key":"b32","series-title":"J Neurotrauma","first-page":"766","article-title":"Interstitial F2-isoprostane 8-iso-PGF2\u03b1 as a biomarker of oxidative stress after severe human traumatic brain injury","volume":"29","author":"Clausen F","year":"2012","unstructured":"Clausen F, Marklund N, Lew\u00e9n A, Enblad P, Basu S, Hillered L. Interstitial F2-isoprostane 8-iso-PGF2\u03b1 as a biomarker of oxidative stress after severe human traumatic brain injury. J Neurotrauma. 2012;29(5):766-775."},{"issue":"5","key":"b33","series-title":"Pediatr Res","first-page":"571","article-title":"Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children","volume":"51","author":"Bayir H","year":"2002","unstructured":"Bayir H, Kagan VE, Tyurina YY, Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatr Res. 2002;51(5):571\u2013578."},{"issue":"7","key":"b34","series-title":"Int J Neurosci","first-page":"700","article-title":"Protective effects of early exercise on neuroinflammation, and neurotoxicity associated by traumatic brain injury: a behavioral and neurochemical approach","volume":"134","author":"Rafie F","year":"2024","unstructured":"Rafie F, Khaksari M, Amiresmaili S, Protective effects of early exercise on neuroinflammation, and neurotoxicity associated by traumatic brain injury: a behavioral and neurochemical approach. Int J Neurosci. 2024;134(7):700\u2013713."},{"issue":"6","key":"b35","series-title":"Brain","first-page":"2064","article-title":"Post-acute blood biomarkers and disease progression in traumatic brain injury","volume":"145","author":"Newcombe VFJ","year":"2022","unstructured":"Newcombe VFJ, Ashton NJ, Posti JP, Post-acute blood biomarkers and disease progression in traumatic brain injury. Brain. 2022;145(6):2064-2076."},{"issue":"8","key":"b36","series-title":"J Neurotrauma","first-page":"1000","article-title":"Traumatic optic nerve injury elevates plasma biomarkers of traumatic brain injury in a porcine model","volume":"38","author":"Bramblett GT","year":"2021","unstructured":"Bramblett GT, Harris JN, Scott LL, Holt AW. Traumatic optic nerve injury elevates plasma biomarkers of traumatic brain injury in a porcine model. J Neurotrauma. 2021;38(8):1000-1005."},{"issue":"11-12","key":"b37","series-title":"J Neurotrauma","first-page":"1353","article-title":"Diagnostic utility of glial fibrillary acidic protein beyond 12 hours after traumatic brain injury: a TRACK-TBI study","volume":"41","author":"Puccio AM","year":"2024","unstructured":"Puccio AM, Yue JK, Korley FK, Diagnostic utility of glial fibrillary acidic protein beyond 12 hours after traumatic brain injury: a TRACK-TBI study. J Neurotrauma. 2024;41(11-12):1353\u20131363."},{"issue":"4","key":"b38","series-title":"Neurosurg Rev","first-page":"2547","article-title":"The prognostic significance of biomarkers in cerebrospinal fluid following severe traumatic brain injury: a systematic review and meta-analysis","volume":"45","author":"Hvingelby VS","year":"2022","unstructured":"Hvingelby VS, Bjarkam CR, Mathiesen TI, The prognostic significance of biomarkers in cerebrospinal fluid following severe traumatic brain injury: a systematic review and meta-analysis. Neurosurg Rev. 2022;45(4):2547-2564."},{"issue":"4","key":"b39","series-title":"Crit Care Med","first-page":"929","article-title":"Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury","volume":"28","author":"Whalen MJ","year":"2000","unstructured":"Whalen MJ, Carlos TM, Kochanek PM, Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury. Crit Care Med. 2000;28(4):929-934."},{"key":"b40","series-title":"Front Immunol","first-page":"604000","article-title":"Sexual dimorphism in innate immunity: the role of sex hormones and epigenetics","volume":"11","author":"Shepherd R","year":"2020","unstructured":"Shepherd R, Cheung AS, Pang K, Saffery R, Novakovic B. Sexual dimorphism in innate immunity: the role of sex hormones and epigenetics. Front Immunol. 2020;11:604000."},{"issue":"4","key":"b1","series-title":"Am J Prev Med","first-page":"754","article-title":"Global burden of traumatic brain injury in 204 countries and territories from 1990 to 2021","volume":"68","author":"Zhong H","year":"2025","unstructured":"Zhong H, Feng Y, Shen J, Global burden of traumatic brain injury in 204 countries and territories from 1990 to 2021. Am J Prev Med. 2025;68(4):754\u2013763."},{"issue":"9","key":"b2","series-title":"Children (Basel)","first-page":"1","article-title":"Burden of traumatic brain injuries in children and adolescents in Europe: hospital discharges, deaths and years of life lost","volume":"2022","author":"Majdan M","unstructured":"Majdan M, Melichova J, Plancikova D, Burden of traumatic brain injuries in children and adolescents in Europe: hospital discharges, deaths and years of life lost. Children (Basel). 2022;(9):1."},{"issue":"11","key":"b3","series-title":"Am J Public Health","first-page":"2074","article-title":"Incidence of disability among children 12 months after traumatic brain injury","volume":"102","author":"Rivara FP","year":"2012","unstructured":"Rivara FP, Koepsell TD, Wang J, Incidence of disability among children 12 months after traumatic brain injury. Am J Public Health. 2012;102(11):2074\u20132079."},{"issue":"1 Pt 2","key":"b4","series-title":"Am J Physiol","first-page":"R135","article-title":"Eicosanoids in third ventricular cerebrospinal fluid of fetal and newborn sheep","volume":"264","author":"Jones SA","year":"1993","unstructured":"Jones SA, Adamson SL, Bishai I, Lees J, Engelberts D, Coceani F. Eicosanoids in third ventricular cerebrospinal fluid of fetal and newborn sheep. Am J Physiol. 1993;264(1 Pt 2):R135-R142."},{"key":"b5","series-title":"Sci Transl Med","first-page":"eabd5758","article-title":"Importance of the pig as a human biomedical model","volume":"13(621)","author":"Lunney JK","year":"2021","unstructured":"Lunney JK, Van Goor A, Walker KE, Hailstock T, Franklin J, Dai C. Importance of the pig as a human biomedical model. Sci Transl Med. 2021;13(621):eabd5758."},{"issue":"3","key":"b6","series-title":"Neural Regen Res","first-page":"413","article-title":"The pig as a preclinical traumatic brain injury model: current models, functional outcome measures, and translational detection strategies","volume":"14","author":"Kinder HA","year":"2019","unstructured":"Kinder HA, Baker EW, West FD. The pig as a preclinical traumatic brain injury model: current models, functional outcome measures, and translational detection strategies. Neural Regen Res. 2019;14(3):413-424."},{"issue":"4","key":"b7","series-title":"Dev Neurosci","first-page":"291","article-title":"Brain growth of the domestic pig (Sus scrofa) from 2 to 24 weeks of age: a longitudinal MRI study","volume":"34","author":"Conrad MS","year":"2012","unstructured":"Conrad MS, Dilger RN, Johnson RW. Brain growth of the domestic pig (Sus scrofa) from 2 to 24 weeks of age: a longitudinal MRI study. Dev Neurosci. 2012;34(4):291-298."},{"issue":"21-22","key":"b8","series-title":"J Neurotrauma","first-page":"2270","article-title":"Pediatric moderate and severe traumatic brain injury: a systematic review of clinical practice guideline recommendations","volume":"40","author":"Ben Abdeljelil A","year":"2023","unstructured":"Ben Abdeljelil A, Freire GC, Yanchar N, Pediatric moderate and severe traumatic brain injury: a systematic review of clinical practice guideline recommendations. J Neurotrauma. 2023;40(21-22):2270-2281."},{"issue":"10","key":"b9","series-title":"Childs Nerv Syst","first-page":"1693","article-title":"Pre-clinical models in pediatric traumatic brain injury-challenges and lessons learned","volume":"33","author":"Kochanek PM","year":"2017","unstructured":"Kochanek PM, Wallisch JS, Bay\u0131r H, Clark RSB. Pre-clinical models in pediatric traumatic brain injury-challenges and lessons learned. Childs Nerv Syst. 2017;33(10):1693-1701."},{"key":"b10","series-title":"J Neuroinflammation","first-page":"40","article-title":"Disruption of Midkine gene reduces traumatic brain injury through the modulation of neuroinflammation","volume":"17(1)","author":"Takada S","year":"2020","unstructured":"Takada S, Sakakima H, Matsuyama T, Disruption of Midkine gene reduces traumatic brain injury through the modulation of neuroinflammation. J Neuroinflammation. 2020;17(1):40."},{"issue":"4","key":"b11","series-title":"Pediatr Neurol","first-page":"227","article-title":"Selective vulnerability in the developing central nervous system","volume":"30","author":"McQuillen PS","year":"2004","unstructured":"McQuillen PS, Ferriero DM. Selective vulnerability in the developing central nervous system. Pediatr Neurol. 2004;30(4):227\u2013235."},{"issue":"5","key":"b12","series-title":"J Agric Food Chem","first-page":"1647","article-title":"Antioxidant activity of docosahexaenoic acid (DHA) and its regulatory roles in mitochondria","volume":"69","author":"Li G","year":"2021","unstructured":"Li G, Li Y, Xiao B, Antioxidant activity of docosahexaenoic acid (DHA) and its regulatory roles in mitochondria. J Agric Food Chem. 2021;69(5):1647\u20131655."},{"issue":"3","key":"b13","series-title":"J Neurosci Res","first-page":"575","article-title":"Docosahexaenoic acid modulates inflammatory and antineurogenic functions of activated microglial cells","volume":"90","author":"Antonietta Ajmone-Cat M","year":"2012","unstructured":"Antonietta Ajmone-Cat M, Lavinia Salvatori M, De Simone R, Docosahexaenoic acid modulates inflammatory and antineurogenic functions of activated microglial cells. J Neurosci Res. 2012;90(3):575-587."},{"issue":"4","key":"b14","series-title":"J Neurotrauma","first-page":"390","article-title":"Dietary docosahexaenoic acid improves cognitive function, tissue sparing, and magnetic resonance imaging indices of edema and white matter injury in the immature rat after traumatic brain injury","volume":"33","author":"Schober ME","year":"2016","unstructured":"Schober ME, Requena DF, Abdullah OM, Dietary docosahexaenoic acid improves cognitive function, tissue sparing, and magnetic resonance imaging indices of edema and white matter injury in the immature rat after traumatic brain injury. J Neurotrauma. 2016;33(4):390-402."},{"key":"b15","series-title":"Exp Neurol","first-page":"112971","article-title":"Docosahexaenoic acid decreased neuroinflammation in rat pups after controlled cortical impact","volume":"320","author":"Schober ME","year":"2019","unstructured":"Schober ME, Requena DF, Casper TC, Docosahexaenoic acid decreased neuroinflammation in rat pups after controlled cortical impact. Exp Neurol. 2019;320:112971."},{"issue":"1","key":"b16","series-title":"Fluids Barriers CNS","first-page":"49","article-title":"A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments","volume":"18","author":"McAllister JP","year":"2021","unstructured":"McAllister JP, Talcott MR, Isaacs AM, A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments. Fluids Barriers CNS. 2021;18(1):49."},{"issue":"1-2","key":"b17","series-title":"Brain Res Bull","first-page":"1","article-title":"Stereotaxic atlas of the pig brain","volume":"49","author":"F\u00e9lix B","year":"1999","unstructured":"F\u00e9lix B, L\u00e9ger ME, Albe-Fessard D, Marcilloux JC, Rampin O, Laplace JP. Stereotaxic atlas of the pig brain. Brain Res Bull. 1999;49(1-2):1\u2013137."},{"issue":"1","key":"b18","series-title":"Int J Dev Neurosci","first-page":"31","article-title":"Effects of lateral fluid percussion injury on cholinergic markers in the newborn piglet brain","volume":"28","author":"Donat CK","year":"2010","unstructured":"Donat CK, Walter B, Kayser T, Effects of lateral fluid percussion injury on cholinergic markers in the newborn piglet brain. Int J Dev Neurosci. 2010;28(1):31-38."},{"issue":"8","key":"b19","series-title":"J Neurotrauma","first-page":"1076","article-title":"Age-dependent effects of severe traumatic brain injury on cerebral dopaminergic activity in newborn and juvenile pigs","volume":"21","author":"Walter B","year":"2004","unstructured":"Walter B, Brust P, F\u00fcchtner F, Age-dependent effects of severe traumatic brain injury on cerebral dopaminergic activity in newborn and juvenile pigs. J Neurotrauma. 2004;21(8):1076\u20131089."},{"issue":"1","key":"b20","series-title":"Sci Rep","first-page":"15907","article-title":"Early weaning and biological sex shape long-term immune and metabolic responses in pigs","volume":"13","author":"Fardisi M","year":"2023","unstructured":"Fardisi M, Thelen K, Groenendal A, Early weaning and biological sex shape long-term immune and metabolic responses in pigs. Sci Rep. 2023;13(1):15907."},{"issue":"2","key":"b21","series-title":"J Reprod Fertil","first-page":"377","article-title":"Changes in serum testosterone concentrations in the male pig during development","volume":"53","author":"Colenbrander B","year":"1978","unstructured":"Colenbrander B, de Jong FH, Wensing CJ. Changes in serum testosterone concentrations in the male pig during development. J Reprod Fertil. 1978;53(2):377\u2013380."},{"issue":"3","key":"b22","series-title":"J Neurotrauma","first-page":"359","article-title":"Craniotomy: true sham for traumatic brain injury, or a sham of a sham?","volume":"28","author":"Cole JT","year":"2011","unstructured":"Cole JT, Yarnell A, Kean WS, Craniotomy: true sham for traumatic brain injury, or a sham of a sham?. J Neurotrauma. 2011;28(3):359\u2013369."},{"issue":"2","key":"b23","series-title":"Can J Anim Sci","first-page":"457","article-title":"An efficient method for collecting urine from neonatal pigs","volume":"59","author":"Parker RO","year":"1979","unstructured":"Parker RO, Williams PEV, Aherne FX, Young BA. An efficient method for collecting urine from neonatal pigs. Can J Anim Sci. 1979;59(2):457\u2013458."},{"issue":"6","key":"b24","series-title":"Med Sci Sports Exerc","first-page":"974","article-title":"Effect of docosahexaenoic acid on a biomarker of head trauma in American football","volume":"48","author":"Oliver JM","year":"2016","unstructured":"Oliver JM, Jones MT, Kirk KM, Effect of docosahexaenoic acid on a biomarker of head trauma in American football. Med Sci Sports Exerc. 2016;48(6):974-982."},{"issue":"2-3","key":"b25","series-title":"Prostaglandins Leukot Essent Fatty Acids","first-page":"125","article-title":"Toxicology and safety of DHA","volume":"81","author":"Lien EL","year":"2009","unstructured":"Lien EL. Toxicology and safety of DHA. Prostaglandins Leukot Essent Fatty Acids. 2009;81(2-3):125-132."},{"issue":"10","key":"b26","series-title":"J Neurotrauma","first-page":"1185","article-title":"Valproic acid treatment decreases serum glial fibrillary acidic protein and neurofilament light chain levels in swine subjected to traumatic brain injury","volume":"35","author":"Korley FK","year":"2018","unstructured":"Korley FK, Nikolian VC, Williams AM, Dennahy IS, Weykamp M, Alam HB. Valproic acid treatment decreases serum glial fibrillary acidic protein and neurofilament light chain levels in swine subjected to traumatic brain injury. J Neurotrauma. 2018;35(10):1185-1191."},{"issue":"9","key":"b27","series-title":"Lancet Neurol","first-page":"782","article-title":"Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study","volume":"17","author":"Bazarian JJ","year":"2018","unstructured":"Bazarian JJ, Biberthaler P, Welch RD, Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018;17(9):782\u2013789."},{"key":"b28","series-title":"EBioMedicine","first-page":"102785","article-title":"Blood biomarkers on admission in acute traumatic brain injury: relations to severity, CT findings and care path in the CENTER-TBI study","volume":"56","author":"Czeiter E","year":"2020","unstructured":"Czeiter E, Amrein K, Gravesteijn BY, Blood biomarkers on admission in acute traumatic brain injury: relations to severity, CT findings and care path in the CENTER-TBI study. EBioMedicine. 2020;56:102785."},{"issue":"1","key":"b29","series-title":"Pediatr Crit Care Med","first-page":"4","article-title":"Biochemical, cellular, and molecular mechanisms in the evolution of secondary damage after severe traumatic brain injury in infants and children: lessons learned from the bedside","volume":"1","author":"Kochanek PM","year":"2000","unstructured":"Kochanek PM, Clark RSB, Ruppel RA, Biochemical, cellular, and molecular mechanisms in the evolution of secondary damage after severe traumatic brain injury in infants and children: lessons learned from the bedside. Pediatr Crit Care Med. 2000;1(1):4\u201319."},{"issue":"15-16","key":"b30","series-title":"J Neurotrauma","first-page":"1914","article-title":"Distinct serum glial fibrillary acidic protein and neurofilament light time-courses after rapid head rotations","volume":"41","author":"Huber CM","year":"2024","unstructured":"Huber CM, Thakore AD, Oeur RA, Margulies SS. Distinct serum glial fibrillary acidic protein and neurofilament light time-courses after rapid head rotations. J Neurotrauma. 2024;41(15-16):1914-1928."},{"issue":"2","key":"b31","series-title":"J Perinat Med","first-page":"209","article-title":"DHA reduces oxidative stress following hypoxia-ischemia in newborn piglets: a study of lipid peroxidation products in urine and plasma","volume":"46","author":"Huun MU","year":"2018","unstructured":"Huun MU, Garberg HT, Escobar J, DHA reduces oxidative stress following hypoxia-ischemia in newborn piglets: a study of lipid peroxidation products in urine and plasma. J Perinat Med. 2018;46(2):209-217."},{"issue":"5","key":"b32","series-title":"J Neurotrauma","first-page":"766","article-title":"Interstitial F2-isoprostane 8-iso-PGF2\u03b1 as a biomarker of oxidative stress after severe human traumatic brain injury","volume":"29","author":"Clausen F","year":"2012","unstructured":"Clausen F, Marklund N, Lew\u00e9n A, Enblad P, Basu S, Hillered L. Interstitial F2-isoprostane 8-iso-PGF2\u03b1 as a biomarker of oxidative stress after severe human traumatic brain injury. J Neurotrauma. 2012;29(5):766-775."},{"issue":"5","key":"b33","series-title":"Pediatr Res","first-page":"571","article-title":"Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children","volume":"51","author":"Bayir H","year":"2002","unstructured":"Bayir H, Kagan VE, Tyurina YY, Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatr Res. 2002;51(5):571\u2013578."},{"issue":"7","key":"b34","series-title":"Int J Neurosci","first-page":"700","article-title":"Protective effects of early exercise on neuroinflammation, and neurotoxicity associated by traumatic brain injury: a behavioral and neurochemical approach","volume":"134","author":"Rafie F","year":"2024","unstructured":"Rafie F, Khaksari M, Amiresmaili S, Protective effects of early exercise on neuroinflammation, and neurotoxicity associated by traumatic brain injury: a behavioral and neurochemical approach. Int J Neurosci. 2024;134(7):700\u2013713."},{"issue":"6","key":"b35","series-title":"Brain","first-page":"2064","article-title":"Post-acute blood biomarkers and disease progression in traumatic brain injury","volume":"145","author":"Newcombe VFJ","year":"2022","unstructured":"Newcombe VFJ, Ashton NJ, Posti JP, Post-acute blood biomarkers and disease progression in traumatic brain injury. Brain. 2022;145(6):2064-2076."},{"issue":"8","key":"b36","series-title":"J Neurotrauma","first-page":"1000","article-title":"Traumatic optic nerve injury elevates plasma biomarkers of traumatic brain injury in a porcine model","volume":"38","author":"Bramblett GT","year":"2021","unstructured":"Bramblett GT, Harris JN, Scott LL, Holt AW. Traumatic optic nerve injury elevates plasma biomarkers of traumatic brain injury in a porcine model. J Neurotrauma. 2021;38(8):1000-1005."},{"issue":"11-12","key":"b37","series-title":"J Neurotrauma","first-page":"1353","article-title":"Diagnostic utility of glial fibrillary acidic protein beyond 12 hours after traumatic brain injury: a TRACK-TBI study","volume":"41","author":"Puccio AM","year":"2024","unstructured":"Puccio AM, Yue JK, Korley FK, Diagnostic utility of glial fibrillary acidic protein beyond 12 hours after traumatic brain injury: a TRACK-TBI study. J Neurotrauma. 2024;41(11-12):1353\u20131363."},{"issue":"4","key":"b38","series-title":"Neurosurg Rev","first-page":"2547","article-title":"The prognostic significance of biomarkers in cerebrospinal fluid following severe traumatic brain injury: a systematic review and meta-analysis","volume":"45","author":"Hvingelby VS","year":"2022","unstructured":"Hvingelby VS, Bjarkam CR, Mathiesen TI, The prognostic significance of biomarkers in cerebrospinal fluid following severe traumatic brain injury: a systematic review and meta-analysis. Neurosurg Rev. 2022;45(4):2547-2564."},{"issue":"4","key":"b39","series-title":"Crit Care Med","first-page":"929","article-title":"Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury","volume":"28","author":"Whalen MJ","year":"2000","unstructured":"Whalen MJ, Carlos TM, Kochanek PM, Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury. Crit Care Med. 2000;28(4):929-934."},{"key":"b40","series-title":"Front Immunol","first-page":"604000","article-title":"Sexual dimorphism in innate immunity: the role of sex hormones and epigenetics","volume":"11","author":"Shepherd R","year":"2020","unstructured":"Shepherd R, Cheung AS, Pang K, Saffery R, Novakovic B. Sexual dimorphism in innate immunity: the role of sex hormones and epigenetics. Front Immunol. 2020;11:604000."}],"container-title":["Journal of Neurosurgery: Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-pediatr\/36\/6\/article-p738.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-pediatr\/36\/6\/article-p738.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-pediatr\/36\/6\/article-p738.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T13:46:20Z","timestamp":1772804780000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-pediatr\/36\/6\/article-p738.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,26]]},"references-count":80,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.3171\/2025.6.peds2555","relation":{},"ISSN":["1933-0707","1933-0715"],"issn-type":[{"value":"1933-0707","type":"print"},{"value":"1933-0715","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,26]]}}}