{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T11:25:22Z","timestamp":1774869922453,"version":"3.50.1"},"reference-count":108,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["PED"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec>\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>Traumatic brain injury (TBI) is a leading cause of death and severe morbidity for otherwise healthy full-term infants around the world. Currently, the primary treatment for infant TBI is supportive, as no targeted therapies exist to actively promote recovery. The developing infant brain, in particular, has a unique response to injury and the potential for repair, both of which vary with maturation. Targeted interventions and objective measures of therapeutic efficacy are needed in this special population. The authors hypothesized that MRI and serum biomarkers can be used to quantify outcomes following infantile TBI in a preclinical rat model and that the potential efficacy of the neuro-reparative agent erythropoietin (EPO) in promoting recovery can be tested using these biomarkers as surrogates for functional outcomes.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>METHODS<\/jats:title>\n<jats:p>With institutional approval, a controlled cortical impact (CCI) was delivered to postnatal Day (P)12 rats of both sexes (76 rats). On postinjury Day (PID)1, the 49 CCI rats designated for chronic studies were randomized to EPO (3000 U\/kg\/dose, CCI-EPO, 24 rats) or vehicle (CCI-veh, 25 rats) administered intraperitoneally on PID1\u20134, 6, and 8. Acute injury (PID3) was evaluated with an immunoassay of injured cortex and serum, and chronic injury (PID13\u201328) was evaluated with digitized gait analyses, MRI, and serum immunoassay. The CCI-veh and CCI-EPO rats were compared with shams (49 rats) primarily using 2-way ANOVA with Bonferroni post hoc correction.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>RESULTS<\/jats:title>\n<jats:p>Following CCI, there was 4.8% mortality and 55% of injured rats exhibited convulsions. Of the injured rats designated for chronic analyses, 8.1% developed leptomeningeal cyst\u2013like lesions verified with MRI and were excluded from further study. On PID3, Western blot showed that EPO receptor expression was increased in the injured cortex (p = 0.008). These Western blots also showed elevated ipsilateral cortex calpain degradation products for \u03b1II-spectrin (\u03b1II-SDPs; p &lt; 0.001), potassium chloride cotransporter 2 (KCC2-DPs; p = 0.037), and glial fibrillary acidic protein (GFAP-DPs; p = 0.002), as well as serum GFAP (serum GFAP-DPs; p = 0.001). In injured rats multiplex electrochemiluminescence analyses on PID3 revealed elevated serum tumor necrosis factor alpha (TNF\u03b1 p = 0.01) and chemokine (CXC) ligand 1 (CXCL1). Chronically, that is, in PID13\u201316 CCI-veh rats, as compared with sham rats, gait deficits were demonstrated (p = 0.033) but then were reversed (p = 0.022) with EPO treatment. Diffusion tensor MRI of the ipsilateral and contralateral cortex and white matter in PID16\u201323 CCI-veh rats showed widespread injury and significant abnormalities of functional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD); MD, AD, and RD improved after EPO treatment. Chronically, P13\u2013P28 CCI-veh rats also had elevated serum CXCL1 levels, which normalized in CCI-EPO rats.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>CONCLUSIONS<\/jats:title>\n<jats:p>Efficient translation of emerging neuro-reparative interventions dictates the use of age-appropriate preclinical models with human clinical trial\u2013compatible biomarkers. In the present study, the authors showed that CCI produced chronic gait deficits in P12 rats that resolved with EPO treatment and that chronic imaging and serum biomarkers correlated with this improvement.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2015.10.peds15554","type":"journal-article","created":{"date-parts":[[2016,2,19]],"date-time":"2016-02-19T14:57:49Z","timestamp":1455893869000},"page":"739-755","source":"Crossref","is-referenced-by-count":33,"title":["Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury"],"prefix":"10.3171","volume":"17","author":[{"given":"Shenandoah","family":"Robinson","sequence":"first","affiliation":[{"name":"Brain Injury Center and\u00a0"},{"name":"Departments of Neurosurgery,"},{"name":"Neurology,"},{"name":"F. M. Kirby Center for Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; and\u00a0"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse L.","family":"Winer","sequence":"additional","affiliation":[{"name":"Brain Injury Center and\u00a0"},{"name":"Departments of Neurosurgery,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Berkner","sequence":"additional","affiliation":[{"name":"Brain Injury Center and\u00a0"},{"name":"Emergency Medicine,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay A. S.","family":"Chan","sequence":"additional","affiliation":[{"name":"Brain Injury Center and\u00a0"},{"name":"Departments of Neurosurgery,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse L.","family":"Denson","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessie R.","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yirong","family":"Yang","sequence":"additional","affiliation":[{"name":"Neurology, University of New Mexico School of Medicine, Albuquerque, New Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurel O.","family":"Sillerud","sequence":"additional","affiliation":[{"name":"Neurology, University of New Mexico School of Medicine, Albuquerque, New Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert C.","family":"Tasker","sequence":"additional","affiliation":[{"name":"Brain Injury Center and\u00a0"},{"name":"Neurology,"},{"name":"Anesthesiology,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William P.","family":"Meehan","sequence":"additional","affiliation":[{"name":"Brain Injury Center and\u00a0"},{"name":"Sports Medicine, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebekah","family":"Mannix","sequence":"additional","affiliation":[{"name":"Brain Injury Center and\u00a0"},{"name":"Emergency Medicine,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren L.","family":"Jantzie","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics,"},{"name":"Neurosciences, and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1-peds15554","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1089\/neu.1997.14.99","article-title":"Motor and cognitive functional deficits following diffuse traumatic brain injury in the immature rat","volume":"14","author":"Adelson","year":"1997"},{"key":"b2-peds15554","series-title":"Childs Nerv Syst","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s00381-012-1932-4","article-title":"Morris water maze function and histologic characterization of two age-at-injury experimental models of controlled cortical impact in the immature rat","volume":"29","author":"Adelson","year":"2013"},{"key":"b3-peds15554","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"877","DOI":"10.3171\/jns.1996.85.5.0877","article-title":"A model of diffuse traumatic brain injury in the immature rat","volume":"85","author":"Adelson","year":"1996"},{"key":"b4-peds15554","series-title":"Turk Neurosurg","first-page":"552","article-title":"Neuroprotective effects of erythropoietin in patients with severe closed brain injury","volume":"25","author":"Aloizos","year":"2015"},{"key":"b5-peds15554","series-title":"Neuroimage Clin","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.nicl.2015.03.021","article-title":"Tract shape modeling detects changes associated with preterm birth and neuroprotective treatment effects","volume":"8","author":"Anblagan","year":"2015"},{"key":"b6-peds15554","series-title":"Childs Nerv Syst","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1007\/s00381-012-1863-0","article-title":"Posttraumatic seizures in children with severe traumatic brain injury","volume":"28","author":"Arango","year":"2012"},{"key":"b7-peds15554","series-title":"Imaging Med","doi-asserted-by":"publisher","first-page":"427","DOI":"10.2217\/iim.13.49","article-title":"Diffusion tensor MRI as a biomarker in axonal and myelin damage","volume":"5","author":"Aung","year":"2013"},{"key":"b8-peds15554","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1089\/neu.2011.1989","article-title":"Serum concentrations of ubiquitin C-terminal hydrolase-L1 and \u03b1II-spectrin breakdown product 145 kDa correlate with outcome after pediatric TBI","volume":"29","author":"Berger","year":"2012"},{"key":"b9-peds15554","series-title":"Pflugers Arch","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1007\/s00424-014-1547-6","article-title":"K-Cl cotransporter KCC2\u2014a moon-lighting protein in excitatory and inhibitory synapse development and function","volume":"467","author":"Blaesse","year":"2015"},{"key":"b10-peds15554","series-title":"Neurosci Biobehav Rev","article-title":"Found in translation: understanding the biology and behavior of experimental traumatic brain injury","author":"Bondi","year":"2014"},{"key":"b11-peds15554","series-title":"Neurobiol Dis","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.nbd.2006.09.002","article-title":"Brain injury impairs dentate gyrus inhibitory efficacy","volume":"25","author":"Bonislawski","year":"2007"},{"key":"b12-peds15554","series-title":"Nat Med","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/nm.2107","article-title":"Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury","volume":"16","author":"Boulenguez","year":"2010"},{"key":"b13-peds15554","series-title":"J Neurotrauma","article-title":"Serum glial fibrillary acidic protein predicts tissue glial fibrillary acidic protein break-down products and therapeutic efficacy after penetrating ballistic-like brain injury","author":"Boutt\u00e9","year":"2015"},{"key":"b14-peds15554","series-title":"Nat Rev Neurosci","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1038\/nrn1687","article-title":"Emerging biological roles for erythropoietin in the nervous system","volume":"6","author":"Brines","year":"2005"},{"key":"b15-peds15554","series-title":"Glia","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1002\/glia.22730","article-title":"GABAergic disinhibition and impaired KCC2 cotransporter activity underlie tumor-associated epilepsy","volume":"63","author":"Campbell","year":"2015"},{"key":"b16-peds15554","series-title":"Exp Neurol","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.expneurol.2014.05.014","article-title":"Chemokine CXCL1 enhances inflammatory pain and increases NMDA receptor activity and COX-2 expression in spinal cord neurons via activation of CXCR2","volume":"261","author":"Cao","year":"2014"},{"key":"b17-peds15554","series-title":"Dev Neurosci","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1159\/000355874","article-title":"Traumatic injury to the immature frontal lobe: a new murine model of long-term motor impairment in the absence of psychosocial or cognitive deficits","volume":"35","author":"Chen","year":"2013"},{"key":"b18-peds15554","series-title":"Neuroimage Clin","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.nicl.2015.02.002","article-title":"White matter disruption in moderate\/severe pediatric traumatic brain injury: advanced tract-based analyses","volume":"7","author":"Dennis","year":"2015"},{"key":"b19-peds15554","series-title":"PLoS One","doi-asserted-by":"publisher","first-page":"e0121541","DOI":"10.1371\/journal.pone.0121541","article-title":"Oligodendrocyte birth and death following traumatic brain injury in adult mice","volume":"10","author":"Dent","year":"2015"},{"key":"b20-peds15554","series-title":"Front Neurol","first-page":"110","article-title":"Blood biomarkers in moderate-to-severe traumatic brain injury: potential utility of a multi-marker approach in characterizing outcome","volume":"6","author":"Di Battista","year":"2015"},{"key":"b21-peds15554","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1089\/neu.2013.3040","article-title":"Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein","volume":"31","author":"Diaz-Arrastia","year":"2014"},{"key":"b22-peds15554","series-title":"J Biomech","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.jbiomech.2003.06.002","article-title":"Mechanical and metabolic requirements for active lateral stabilization in human walking","volume":"37","author":"Donelan","year":"2004"},{"key":"b23-peds15554","series-title":"Stem Cells","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1634\/stemcells.2007-0753","article-title":"Alpha-chemokines regulate proliferation, neurogenesis, and dopaminergic differentiation of ventral midbrain precursors and neurospheres","volume":"26","author":"Edman","year":"2008"},{"key":"b24-peds15554","series-title":"Pediatrics","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1542\/peds.2007-2591","article-title":"An approach to using recombinant erythropoietin for neuroprotection in very preterm infants","volume":"122","author":"Fauch\u00e8re","year":"2008"},{"key":"b25-peds15554","series-title":"J Pediatr","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jpeds.2015.02.052","article-title":"Safety of early high-dose recombinant erythropoietin for neuroprotection in very preterm infants","volume":"167","author":"Fauch\u00e8re","year":"2015"},{"key":"b26-peds15554","series-title":"Pediatr Crit Care Med","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1097\/PCC.0b013e3181e8b32d","article-title":"Severe traumatic brain injury in children elevates glial fibrillary acidic protein in cerebrospinal fluid and serum","volume":"12","author":"Fraser","year":"2011"},{"key":"b27-peds15554","series-title":"Childs Nerv Syst","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1007\/s00381-007-0345-2","article-title":"Diffuse alterations in synaptic protein expression following focal traumatic brain injury in the immature rat","volume":"23","author":"Gobbel","year":"2007"},{"key":"b28-peds15554","series-title":"Exp Neurol","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.expneurol.2015.02.029","article-title":"Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats","volume":"267","author":"Gu","year":"2015"},{"key":"b29-peds15554","series-title":"J Neuroinflammation","first-page":"156","article-title":"Erythropoietin improves motor and cognitive deficit, axonal pathology, and neuroinflammation in a combined model of diffuse traumatic brain injury and hypoxia, in association with upregulation of the erythropoietin receptor","volume":"10","author":"Hellewell","year":"2013"},{"key":"b30-peds15554","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1089\/neu.2015.3873","article-title":"Acute temporal profiles of serum levels of UCH-L1 and GFAP and relationships to neuronal and astroglial pathology following traumatic brain injury in rats","volume":"32","author":"Huang","year":"2015"},{"key":"b31-peds15554","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"9866","DOI":"10.1523\/JNEUROSCI.2761-07.2007","article-title":"Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy","volume":"27","author":"Huberfeld","year":"2007"},{"key":"b32-peds15554","series-title":"Neuron","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/S0896-6273(01)00297-5","article-title":"Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition","volume":"30","author":"H\u00fcbner","year":"2001"},{"key":"b33-peds15554","series-title":"Semin Fetal Neonatal Med","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.siny.2006.07.006","article-title":"Diffusion tensor imaging of brain development","volume":"11","author":"H\u00fcppi","year":"2006"},{"key":"b34-peds15554","series-title":"J Neuroinflammation","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/1742-2094-11-131","article-title":"Complex pattern of interaction between in utero hypoxia-ischemia and intra-amniotic inflammation disrupts brain development and motor function","volume":"11","author":"Jantzie","year":"2014"},{"key":"b35-peds15554","series-title":"Cereb Cortex","doi-asserted-by":"publisher","first-page":"2683","DOI":"10.1093\/cercor\/bhu066","article-title":"Postnatal erythropoietin mitigates impaired cerebral cortical development following subplate loss from prenatal hypoxia-ischemia","volume":"25","author":"Jantzie","year":"2015"},{"key":"b36-peds15554","series-title":"Front Cell Neurosci","first-page":"347","article-title":"Prenatal hypoxia-ischemia induces abnormalities in CA3 microstructure, potassium chloride co-transporter 2 expression and inhibitory tone","volume":"9","author":"Jantzie","year":"2015"},{"key":"b37-peds15554","series-title":"Mol Cell Neurosci","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.mcn.2014.06.009","article-title":"Erythropoietin attenuates loss of potassium chloride co-transporters following prenatal brain injury","volume":"61","author":"Jantzie","year":"2014"},{"key":"b38-peds15554","series-title":"Pediatr Res","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1038\/pr.2013.155","article-title":"Erythropoietin signaling promotes oligodendrocyte development following prenatal systemic hypoxic-ischemic brain injury","volume":"74","author":"Jantzie","year":"2013"},{"key":"b39-peds15554","series-title":"Dev Neurosci","article-title":"Erythropoietin modulates cerebral and serum degradation products from excess calpain activation following prenatal hypoxia-ischemia","author":"Jantzie","year":"2015"},{"key":"b40-peds15554","series-title":"Pediatrics","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1542\/peds.2007-2711","article-title":"A phase I\/II trial of high-dose erythropoietin in extremely low birth weight infants: pharmacokinetics and safety","volume":"122","author":"Juul","year":"2008"},{"key":"b41-peds15554","series-title":"Neurobiol Dis","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.nbd.2006.07.007","article-title":"Erythropoietin is neuroprotective against NMDA-receptor-mediated excitotoxic brain injury in newborn mice","volume":"24","author":"Keller","year":"2006"},{"key":"b42-peds15554","series-title":"Pediatr Res","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1203\/pdr.0b013e3180332cec","article-title":"A comparison of high-dose recombinant erythropoietin treatment regimens in brain-injured neonatal rats","volume":"61","author":"Kellert","year":"2007"},{"key":"b43-peds15554","series-title":"Anat Embryol (Berl)","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1007\/s00429-003-0365-y","article-title":"Expression patterns of erythropoietin and its receptor in the developing midbrain","volume":"207","author":"Knabe","year":"2004"},{"key":"b44-peds15554","series-title":"Anat Embryol (Berl)","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s00429-005-0019-3","article-title":"Expression patterns of erythropoietin and its receptor in the developing spinal cord and dorsal root ganglia","volume":"210","author":"Knabe","year":"2005"},{"key":"b45-peds15554","series-title":"Brain Dev","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.braindev.2011.04.003","article-title":"Etiological analysis of presumed perinatal stroke","volume":"34","author":"Kocaman","year":"2012"},{"key":"b46-peds15554","series-title":"JAMA","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1001\/jama.2014.9645","article-title":"Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age","volume":"312","author":"Leuchter","year":"2014"},{"key":"b47-peds15554","series-title":"Pediatrics","doi-asserted-by":"publisher","first-page":"e104","DOI":"10.1542\/peds.2009-1076","article-title":"Fractures and traumatic brain injuries: abuse versus accidents in a US database of hospitalized children","volume":"126","author":"Leventhal","year":"2010"},{"key":"b48-peds15554","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"11869","DOI":"10.1523\/JNEUROSCI.3647-07.2007","article-title":"Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury","volume":"27","author":"Mac Donald","year":"2007"},{"key":"b49-peds15554","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.3171\/2014.8.JNS14715","article-title":"Sex differences in the effect of progesterone after controlled cortical impact in adolescent mice: a preliminary study","volume":"121","author":"Mannix","year":"2014"},{"key":"b50-peds15554","series-title":"Brain Inj","doi-asserted-by":"publisher","first-page":"743","DOI":"10.3109\/02699052.2013.771797","article-title":"Beneficial effect of amyloid beta after controlled cortical impact","volume":"27","author":"Mannix","year":"2013"},{"key":"b51-peds15554","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1089\/neu.2011.1759","article-title":"Detrimental effect of genetic inhibition of B-site APP-cleaving enzyme 1 on functional outcome after controlled cortical impact in young adult mice","volume":"28","author":"Mannix","year":"2011"},{"key":"b52-peds15554","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/jcbfm.2010.99","article-title":"Age-dependent effect of apolipoprotein E4 on functional outcome after controlled cortical impact in mice","volume":"31","author":"Mannix","year":"2011"},{"key":"b53-peds15554","series-title":"J Neurosurg Pediatr","doi-asserted-by":"publisher","first-page":"206","DOI":"10.3171\/2010.5.PEDS1032","article-title":"Postnatal erythropoietin treatment mitigates neural cell loss after systemic prenatal hypoxic-ischemic injury","volume":"6","author":"Mazur","year":"2010"},{"key":"b54-peds15554","series-title":"J Perinatol","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/jp.2012.78","article-title":"Outcomes of extremely low birth weight infants given early high-dose erythropoietin","volume":"33","author":"McAdams","year":"2013"},{"key":"b55-peds15554","series-title":"Brain Inj","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1080\/02699050801888824","article-title":"Prevalence of traumatic brain injury among children, adolescents and young adults: prospective evidence from a birth cohort","volume":"22","author":"McKinlay","year":"2008"},{"key":"b56-peds15554","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1089\/neu.2014.3635","article-title":"Measurement of the glial fibrillary acidic protein and its breakdown products GFAP-BDP biomarker for the detection of traumatic brain injury compared to computed tomography and magnetic resonance imaging","volume":"32","author":"McMahon","year":"2015"},{"key":"b57-peds15554","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"550","DOI":"10.3171\/2011.3.JNS101721","article-title":"Dose-dependent neurorestorative effects of delayed treatment of traumatic brain injury with recombinant human erythropoietin in rats","volume":"115","author":"Meng","year":"2011"},{"key":"b58-peds15554","series-title":"Lancet Neurol","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1016\/S1474-4422(09)70257-1","article-title":"Imaging biomarkers of outcome in the developing preterm brain","volume":"8","author":"Ment","year":"2009"},{"key":"b59-peds15554","series-title":"Pediatrics","doi-asserted-by":"publisher","first-page":"e1545","DOI":"10.1542\/peds.2014-1385","article-title":"Disability-adjusted life-year burden of abusive head trauma at ages 0\u20134","volume":"134","author":"Miller","year":"2014"},{"key":"b60-peds15554","series-title":"J Clin Psychiatry","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.4088\/JCP.13m08839","article-title":"Recombinant human erythropoietin to target cognitive dysfunction in bipolar disorder: a double-blind, randomized, placebo-controlled phase 2 trial","volume":"75","author":"Miskowiak","year":"2014"},{"key":"b61-peds15554","series-title":"Neuropsychopharmacology","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1038\/npp.2013.335","article-title":"Recombinant human erythropoietin for treating treatment-resistant depression: a double-blind, randomized, placebo-controlled phase 2 trial","volume":"39","author":"Miskowiak","year":"2014"},{"key":"b62-peds15554","series-title":"Inj Prev","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1136\/ip.2009.021550","article-title":"Recent trends in television tip over-related injuries among children aged 0\u20139 years","volume":"15","author":"Murray","year":"2009"},{"key":"b63-peds15554","series-title":"Pediatrics","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1542\/peds.2013-4307","article-title":"Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo","volume":"133","author":"Ohls","year":"2014"},{"key":"b64-peds15554","series-title":"J Neurosurg Pediatr","doi-asserted-by":"publisher","first-page":"167","DOI":"10.3171\/2014.12.PEDS14263","article-title":"Incidence of seizures on continuous EEG monitoring following traumatic brain injury in children","volume":"16","author":"O'Neill","year":"2015"},{"key":"b65-peds15554","series-title":"Sci Transl Med","first-page":"244ra89","article-title":"Cortical GABAergic excitation contributes to epileptic activities around human glioma","volume":"6","author":"Pallud","year":"2014"},{"key":"b66-peds15554","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1089\/neu.2014.3655","article-title":"Systematic review of clinical studies examining biomarkers of brain injury in athletes after sports-related concussion","volume":"32","author":"Papa","year":"2015"},{"key":"b67-peds15554","series-title":"Trends Neurosci","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/S0166-2236(03)00068-7","article-title":"Cation-chloride co-transporters in neuronal communication, development and trauma","volume":"26","author":"Payne","year":"2003"},{"key":"b68-peds15554","series-title":"J Physiol","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1113\/jphysiol.2010.203703","article-title":"Knocking down of the KCC2 in rat hippocampal neurons increases intracellular chloride concentration and compromises neuronal survival","volume":"589","author":"Pellegrino","year":"2011"},{"key":"b69-peds15554","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"653","DOI":"10.3171\/2014.6.JNS132577","article-title":"The efficacy of erythropoietin in treating experimental traumatic brain injury: a systematic review of controlled trials in animal models","volume":"121","author":"Peng","year":"2014"},{"key":"b70-peds15554","series-title":"Neuroreport","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.1097\/00001756-199808030-00002","article-title":"Regional calpain and caspase-3 proteolysis of alpha-spectrin after traumatic brain injury","volume":"9","author":"Pike","year":"1998"},{"key":"b71-peds15554","series-title":"Pathophysiology","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.pathophys.2012.02.005","article-title":"Erythropoietin neuroprotection with traumatic brain injury","volume":"20","author":"Ponce","year":"2013"},{"key":"b72-peds15554","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"11356","DOI":"10.1523\/JNEUROSCI.6265-11.2012","article-title":"Activity-dependent cleavage of the K-Cl cotransporter KCC2 mediated by calcium-activated protease calpain","volume":"32","author":"Puskarjov","year":"2012"},{"key":"b73-peds15554","series-title":"N Engl J Med","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1056\/NEJMc1407902","article-title":"Epidemiology of blunt head trauma in children in U.S. emergency departments","volume":"371","author":"Quayle","year":"2014"},{"key":"b74-peds15554","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1089\/neu.2007.3790","article-title":"Diffuse brain injury in the immature rat: evidence for an age-at-injury effect on cognitive function and histopathologic damage","volume":"24","author":"Raghupathi","year":"2007"},{"key":"b75-peds15554","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.1089\/neu.2012.2434","article-title":"Persistence of disability 24 to 36 months after pediatric traumatic brain injury: a cohort study","volume":"29","author":"Rivara","year":"2012"},{"key":"b76-peds15554","series-title":"Nature","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/16697","article-title":"The K+\/Cl\u2212 co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation","volume":"397","author":"Rivera","year":"1999"},{"key":"b77-peds15554","series-title":"JAMA","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1001\/jama.2014.6490","article-title":"Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial","volume":"312","author":"Robertson","year":"2014"},{"key":"b78-peds15554","series-title":"Dev Neurosci","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1159\/000048717","article-title":"Chemokine GRO1 and the spatial and temporal regulation of oligodendrocyte precursor proliferation","volume":"23","author":"Robinson","year":"2001"},{"key":"b79-peds15554","series-title":"J Neuropathol Exp Neurol","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1097\/NEN.0b013e3181dd25bc","article-title":"Loss of cation-chloride cotransporter expression in preterm infants with white matter lesions: implications for the pathogenesis of epilepsy","volume":"69","author":"Robinson","year":"2010"},{"key":"b80-peds15554","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"10457","DOI":"10.1523\/JNEUROSCI.18-24-10457.1998","article-title":"The chemokine growth-regulated oncogene-alpha promotes spinal cord oligodendrocyte precursor proliferation","volume":"18","author":"Robinson","year":"1998"},{"key":"b81-peds15554","series-title":"J Surg Res","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.jss.2010.05.051","article-title":"Traumatic television tip-overs in the pediatric patient population","volume":"166","author":"Rutkoski","year":"2011"},{"key":"b82-peds15554","series-title":"J Neurosurg Pediatr","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3171\/2009.9.PEDS09180","article-title":"Prevention of growing skull fractures: report of 2 cases","volume":"5","author":"Sanford","year":"2010"},{"key":"b83-peds15554","series-title":"Behav Brain Res","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.bbr.2015.02.038","article-title":"Evaluation of gait impairment in mice subjected to craniotomy and traumatic brain injury","volume":"286","author":"Sashindranath","year":"2015"},{"key":"b84-peds15554","series-title":"J Neurotrauma","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","author":"Schober","year":"2015"},{"key":"b85-peds15554","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1089\/neu.2013.2922","article-title":"Erythropoietin improved cognitive function and decreased hippocampal caspase activity in rat pups after traumatic brain injury","volume":"31","author":"Schober","year":"2014"},{"key":"b86-peds15554","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.brainres.2014.05.046","article-title":"Alpha II Spectrin breakdown products in immature Sprague Dawley rat hippocampus and cortex after traumatic brain injury","volume":"1574","author":"Schober","year":"2014"},{"key":"b87-peds15554","series-title":"Prog Neurobiol","first-page":"1","article-title":"Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species","volume":"106\u2013107","author":"Semple","year":"2013"},{"key":"b88-peds15554","series-title":"Neurobiol Dis","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.nbd.2010.06.015","article-title":"Deficiency of the chemokine receptor CXCR2 attenuates neutrophil infiltration and cortical damage following closed head injury","volume":"40","author":"Semple","year":"2010"},{"key":"b89-peds15554","series-title":"PLoS One","doi-asserted-by":"publisher","first-page":"e103386","DOI":"10.1371\/journal.pone.0103386","article-title":"Sociosexual and communication deficits after traumatic injury to the developing murine brain","volume":"9","author":"Semple","year":"2014"},{"key":"b90-peds15554","series-title":"Apoptosis","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1007\/s10495-007-0141-1","article-title":"Protective effect of erythropoietin against ketamine-induced apoptosis in cultured rat cortical neurons: involvement of PI3K\/Akt and GSK-3 beta pathway","volume":"12","author":"Shang","year":"2007"},{"key":"b91-peds15554","series-title":"Brain Struct Funct","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1007\/s00429-013-0683-7","article-title":"Diffusion tensor imaging of hippocampal network plasticity","volume":"220","author":"Sierra","year":"2015"},{"key":"b92-peds15554","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"8291","DOI":"10.1523\/JNEUROSCI.5205-14.2015","article-title":"Selective inhibition of KCC2 leads to hyperexcitability and epileptiform discharges in hippocampal slices and in vivo","volume":"35","author":"Sivakumaran","year":"2015"},{"key":"b93-peds15554","series-title":"Behav Brain Res","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/0166-4328(95)00264-2","article-title":"Traumatic brain injury of the forelimb and hindlimb sensorimotor areas in the rat: physiological, histological and behavioral correlates","volume":"79","author":"Soblosky","year":"1996"},{"key":"b94-peds15554","series-title":"Pediatr Res","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1203\/pdr.0b013e31805341dc","article-title":"Pharmacokinetics of high-dose recombinant erythropoietin in plasma and brain of neonatal rats","volume":"61","author":"Statler","year":"2007"},{"key":"b95-peds15554","series-title":"Dev Neurosci","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1159\/000316806","article-title":"Corpus callosum and inferior forebrain white matter microstructure are related to functional outcome from raised intracranial pressure in child traumatic brain injury","volume":"32","author":"Tasker","year":"2010"},{"key":"b96-peds15554","series-title":"Cell","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/S0092-8674(02)00838-3","article-title":"The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration","volume":"110","author":"Tsai","year":"2002"},{"key":"b97-peds15554","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1523\/JNEUROSCI.4480-05.2006","article-title":"A critical role of erythropoietin receptor in neurogenesis and post-stroke recovery","volume":"26","author":"Tsai","year":"2006"},{"key":"b98-peds15554","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"6554","DOI":"10.1523\/JNEUROSCI.0291-15.2015","article-title":"Closed head injury in an age-related Alzheimer mouse model leads to an altered neuroinflammatory response and persistent cognitive impairment","volume":"35","author":"Webster","year":"2015"},{"key":"b99-peds15554","series-title":"Cell Death Dis","doi-asserted-by":"publisher","first-page":"e1776","DOI":"10.1038\/cddis.2015.127","article-title":"Chloride transporter KCC2-dependent neuroprotection depends on the N-terminal protein domain","volume":"6","author":"Winkelmann","year":"2015"},{"key":"b100-peds15554","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"2609","DOI":"10.1523\/JNEUROSCI.20-07-02609.2000","article-title":"Elevated levels of the chemokine GRO-1 correlate with elevated oligodendrocyte progenitor proliferation in the jimpy mutant","volume":"20","author":"Wu","year":"2000"},{"key":"b101-peds15554","series-title":"Pediatrics","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1542\/peds.2012-0498","article-title":"Erythropoietin for neuroprotection in neonatal encephalopathy: safety and pharmacokinetics","volume":"130","author":"Wu","year":"2012"},{"key":"b102-peds15554","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"598","DOI":"10.3171\/2009.9.JNS09844","article-title":"Delayed administration of erythropoietin reducing hippocampal cell loss, enhancing angiogenesis and neurogenesis, and improving functional outcome following traumatic brain injury in rats: comparison of treatment with single and triple dose","volume":"113","author":"Xiong","year":"2010"},{"key":"b103-peds15554","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"549","DOI":"10.3171\/2010.10.JNS10925","article-title":"Effects of posttraumatic carbamylated erythropoietin therapy on reducing lesion volume and hippocampal cell loss, enhancing angiogenesis and neurogenesis, and improving functional outcome in rats following traumatic brain injury","volume":"114","author":"Xiong","year":"2011"},{"key":"b104-peds15554","series-title":"J Neuroinflammation","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/1742-2094-11-38","article-title":"NF\u03baB-mediated CXCL1 production in spinal cord astrocytes contributes to the maintenance of bone cancer pain in mice","volume":"11","author":"Xu","year":"2014"},{"key":"b105-peds15554","series-title":"CNS Neurosci Ther","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1111\/cns.12127","article-title":"Biomarkers for the clinical differential diagnosis in traumatic brain injury\u2014a systematic review","volume":"19","author":"Yokobori","year":"2013"},{"key":"b106-peds15554","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1089\/neu.2014.3701","article-title":"A new rabbit model of pediatric traumatic brain injury","volume":"32","author":"Zhang","year":"2015"},{"key":"b107-peds15554","series-title":"PLoS One","doi-asserted-by":"publisher","first-page":"e92698","DOI":"10.1371\/journal.pone.0092698","article-title":"Human traumatic brain injury induces auto-antibody response against glial fibrillary acidic protein and its breakdown products","volume":"9","author":"Zhang","year":"2014"},{"key":"b108-peds15554","series-title":"J Biol Chem","doi-asserted-by":"publisher","first-page":"33853","DOI":"10.1074\/jbc.M112.395830","article-title":"N-methyl-D-aspartate receptor- and calpain-mediated proteolytic cleavage of K+-Cl\u2212 cotransporter-2 impairs spinal chloride homeostasis in neuropathic pain","volume":"287","author":"Zhou","year":"2012"}],"container-title":["Journal of Neurosurgery: Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-pediatr\/17\/6\/article-p739.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-pediatr\/17\/6\/article-p739.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-pediatr\/17\/6\/article-p739.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T13:15:23Z","timestamp":1681564523000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-pediatr\/17\/6\/article-p739.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6]]},"references-count":108,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.3171\/2015.10.peds15554","relation":{},"ISSN":["1933-0707","1933-0715"],"issn-type":[{"value":"1933-0707","type":"print"},{"value":"1933-0715","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6]]}}}