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Serum biomarkers of hypoxic-ischemic brain injury

. 2023 Dec 29 ; 72 (S5) : S461-S474.

Language English Country Czech Republic Media print

Document type Journal Article, Review

Brain injury is a multifaceted condition arising from nonspecific damage to nervous tissue. The resulting cognitive developmental impairments reverberate through patients' lives, affecting their families, and even the broader economic landscape. The significance of early brain injury detection lies in its potential to stave off severe consequences and enhance the effectiveness of tailored therapeutic interventions. While established methods like neuroimaging and neurophysiology serve as valuable diagnostic tools, their demanding nature restricts their accessibility, particularly in scenarios such as small hospitals, nocturnal or weekend shifts, and cases involving unstable patients. Hence, there is a pressing need for more accessible and efficient diagnostic avenues. Among the spectrum of brain injuries, hypoxic-ischemic encephalopathy stands out as a predominant affliction in the pediatric population. Diagnosing brain injuries in newborns presents challenges due to the subjective nature of assessments like Apgar scores and the inherent uncertainty in neurological examinations. In this context, methods like magnetic resonance and ultrasound hold recommendations for more accurate diagnosis. Recognizing the potential of serum biomarkers derived from blood samples, this paper underscores their promise as a more expedient and resource-efficient means of assessing brain injuries. The review compiles current insights into serum biomarkers, drawing from experiments conducted on animal models as well as human brain pathologies. The authors aim to elucidate specific characteristics, temporal profiles, and the available corpus of experimental and clinical data for serum biomarkers specific to brain injuries. These include neuron-specific enolase (NSE), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein beta (S100B), glial fibrillary acidic protein (GFAP), and high-mobility-group-protein-box-1 (HMGB1). This comprehensive endeavor contributes to advancing the understanding of brain injury diagnostics and potential avenues for therapeutic intervention.

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Wilde EA, Wanner IB, Kenney K, Gill J, Stone JR, Disner S, Schnakers C, et al. A Framework to Advance Biomarker Development in the Diagnosis, Outcome Prediction, and Treatment of Traumatic Brain Injury. J Neurotrauma. 2022;39:436–457. doi: 10.1089/neu.2021.0099. PubMed DOI PMC

Robb MA, McInnes PM, Califf RM. Biomarkers and Surrogate Endpoints: Developing Common Terminology and Definitions. JAMA. 2016;315:1107–1108. doi: 10.1001/jama.2016.2240. PubMed DOI

Richter S, Winzeck S, Czeiter E, Amrein K, Kornaropoulos EN, Verheyden J, Sugar G, et al. Serum biomarkers identify critically ill traumatic brain injury patients for MRI. Crit Care. 2022;26:369. doi: 10.1186/s13054-022-04250-3. PubMed DOI PMC

Herrera CA, Silver RM. Perinatal Asphyxia from the Obstetric Standpoint: Diagnosis and Interventions. Clin Perinatol. 2016;43:423–438. doi: 10.1016/j.clp.2016.04.003. PubMed DOI

Gururaj A, Sztriha L, Dawodu A, Nath KR, Varady E, Nork M, Haas D. CT and MR patterns of hypoxic ischemic brain damage following perinatal asphyxia. J Trop Pediatr. 2002;48:5–9. doi: 10.1093/tropej/48.1.5. PubMed DOI

McDonald BC, Saykin AJ, McAllister TW. Functional MRI of mild traumatic brain injury (mTBI): progress and perspectives from the first decade of studies. Brain Imaging Behav. 2012;6:193–207. doi: 10.1007/s11682-012-9173-4. PubMed DOI PMC

Alderliesten T, de Vries LS, Staats L, van Haastert IC, Weeke L, Benders MJ, Koopman-Esseboom C, Groenendaal F. MRI and spectroscopy in (near) term neonates with perinatal asphyxia and therapeutic hypothermia. Arch Dis Child Fetal Neonatal Ed. 2017;102:F147–F152. doi: 10.1136/archdischild-2016-310514. PubMed DOI

Roldán M, Kyriacou PA. Near-Infrared Spectroscopy (NIRS) in Traumatic Brain Injury (TBI) Sensors (Basel) 2021;21:1586. doi: 10.3390/s21051586. PubMed DOI PMC

Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976;33:696–705. doi: 10.1001/archneur.1976.00500100030012. PubMed DOI

Bustamante-Hervás C, Valverde E, Vega-Del-Val C, Schuffelmann S, Arnaez J. Inter-observer reliability for amplitude-integrated EEG in the newborn with perinatal asphyxia. (In Spanish) An Pediatr (Engl Ed) 2021 doi: 10.1016/j.anpedi.2021.01.014. S1695-4033(21)00116-8 . PubMed DOI

Lacan L, Betrouni N, Lamblin MD, Chaton L, Delval A, Bourriez JL, Storme L, Derambure P, NguyenThe Tich S. Quantitative approach to early neonatal EEG visual analysis in hypoxic-ischemic encephalopathy severity: Bridging the gap between eyes and machine. Neurophysiol Clin. 2021;51:121–131. doi: 10.1016/j.neucli.2020.12.003. PubMed DOI

Kamino D, Almazrooei A, Pang EW, Widjaja E, Moore AM, Chau V, Tam EWY. Abnormalities in evoked potentials associated with abnormal glycemia and brain injury in neonatal hypoxic-ischemic encephalopathy. Clin Neurophysiol. 2021;132:307–313. doi: 10.1016/j.clinph.2020.09.024. PubMed DOI PMC

Lori S, Bertini G, Bastianelli ME, Gabbanini S, Cossu C, Mortilla M, Dani C. Continuous somatosensory evoked potentials and brain injury in neonatal hypoxic-ischaemic encephalopathy treated with hypothermia. Dev Med Child Neurol. 2022;64:1123–1130. doi: 10.1111/dmcn.15190. PubMed DOI

Jiang ZD, Xu X, Yin R, Shao XM, Wilkinson AR. Differential changes in peripheral and central components of the brain stem auditory evoked potentials during the neonatal period in term infants after perinatal hypoxia-ischemia. Ann Otol Rhinol Laryngol. 2004;113:571–576. doi: 10.1177/000348940411300711. PubMed DOI

Gong X, Zhang H, Liu X, Liu Y, Liu J, Fapohunda FO, Lü P, Wang K, Tang M. Is liquid biopsy mature enough for the diagnosis of Alzheimer's disease? Front Aging Neurosci. 2022;14:977999. doi: 10.3389/fnagi.2022.977999. PubMed DOI PMC

Takano R, Misu T, Takahashi T, Sato S, Fujihara K, Itoyama Y. Astrocytic damage is far more severe than demyelination in NMO: a clinical CSF biomarker study. Neurology. 2010;75:208–216. doi: 10.1212/WNL.0b013e3181e2414b. PubMed DOI

Massaro AN, Wu YW, Bammler TK, Comstock B, Mathur A, McKinstry RC, Chang T, et al. Plasma Biomarkers of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy. J Pediatr. 2018;194:67–75.e1. doi: 10.1016/j.jpeds.2017.10.060. PubMed DOI

Depoorter A, Neumann RP, Barro C, Fisch U, Weber P, Kuhle J, Wellmann S. Neurofilament Light Chain: Blood Biomarker of Neonatal Neuronal Injury. Front Neurol. 2018;9:984. doi: 10.3389/fneur.2018.00984. PubMed DOI PMC

Nakamura T, Asanuma H, Kusuda S, Imai K, Hosono S, Kato R, Suzuki S, et al. Multicenter study for brain/body hypothermia for hypoxic-ischemic encephalopathy: Changes in HMGB-1. Pediatr Int. 2017;59:1074–1079. doi: 10.1111/ped.13377. PubMed DOI

Yan XJ, Zhan CP, Lv Y, Mao DD, Zhou RC, Xv YM, Yu GF. Utility of serum nuclear factor erythroid 2-related factor 2 as a potential prognostic biomarker of severe traumatic brain injury in adults: A prospective cohort study. Front Neurol. 2022;13:1013062. doi: 10.3389/fneur.2022.1013062. PubMed DOI PMC

Cho KHT, Xu B, Blenkiron C, Fraser M. Emerging Roles of miRNAs in Brain Development and Perinatal Brain Injury. Front Physiol. 2019;10:227. doi: 10.3389/fphys.2019.00227. PubMed DOI PMC

Watson CN, Belli A, Di Pietro V. Small Non-coding RNAs: New Class of Biomarkers and Potential Therapeutic Targets in Neurodegenerative Disease. Front Genet. 2019;10:364. doi: 10.3389/fgene.2019.00364. PubMed DOI PMC

Mathew JL, Kaur N, Dsouza JM. Therapeutic hypothermia in neonatal hypoxic encephalopathy: A systematic review and meta-analysis. J Glob Health. 2022;12:04030. doi: 10.7189/jogh.12.04030. PubMed DOI PMC

Ayres-de-Campos D, Spong CY, Chandraharan E FIGO Intrapartum Fetal Monitoring Expert Consensus Panel. FIGO consensus guidelines on intrapartum fetal monitoring: Cardiotocography. Int J Gynaecol Obstet. 2015;131:13–24. doi: 10.1016/j.ijgo.2015.06.020. PubMed DOI

Ghi T, Eggebø T, Lees C, Kalache K, Rozenberg P, Youssef A, Salomon LJ, Tutschek B. ISUOG Practice Guidelines: intrapartum ultrasound. Ultrasound Obstet Gynecol. 2018;52:128–139. doi: 10.1002/uog.19072. PubMed DOI

American Academy Of Pediatrics Committee On Fetus and Newborn And American College Of Obstetricians And Gynecologists Committee On Obstetric Practice. The Apgar Score. Pediatrics. 2015;136:819–822. doi: 10.1542/peds.2015-2651. PubMed DOI

Locatelli A, Lambicchi L, Incerti M, Bonati F, Ferdico M, Malguzzi S, Torcasio F, et al. Is perinatal asphyxia predictable? BMC Pregnancy Childbirth. 2020;20:186. doi: 10.1186/s12884-020-02876-1. PubMed DOI PMC

Ganeshalingham A, Beca J. Serum biomarkers in severe paediatric traumatic brain injury-a narrative review. Transl Pediatr. 2021;10:2720–2737. doi: 10.21037/tp-20-386. PubMed DOI PMC

Riljak V, Kraf J, Daryanani A, Jiruška P, Otáhal J. Pathophysiology of perinatal hypoxic-ischemic encephalopathy - biomarkers, animal models and treatment perspectives. Physiol Res. 2016;65(Suppl 5):S533–S545. doi: 10.33549/physiolres.933541. PubMed DOI

Michetti F, Corvino V, Geloso MC, Lattanzi W, Bernardini C, Serpero L, Gazzolo D. The S100B protein in biological fluids: more than a lifelong biomarker of brain distress. J Neurochem. 2012;120:644–659. doi: 10.1111/j.1471-4159.2011.07612.x. PubMed DOI

Lee Y, Lee BH, Yip W, Chou P, Yip BS. Neurofilament Proteins as Prognostic Biomarkers in Neurological Disorders. Curr Pharm Des. 2020;25:4560–4569. doi: 10.2174/1381612825666191210154535. PubMed DOI

Påhlman S, Esscher T, Bergvall P, Odelstad L. Purification and characterization of human neuron-specific enolase: radioimmunoassay development. Tumour Biol. 1984;5:127–139. PubMed

Thelin EP, Zeiler FA, Ercole A, Mondello S, Büki A, Bellander BM, Helmy A, Menon DK, Nelson DW. Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain Injury Dynamics: A Systematic Review. Front Neurol. 2017;8:300. doi: 10.3389/fneur.2017.00300. PubMed DOI PMC

Brophy GM, Mondello S, Papa L, Robicsek SA, Gabrielli A, Tepas J, Buki A, et al. Biokinetic Analysis of Ubiquitin C-Terminal Hydrolase-L1 UCH-L1 in Severe Traumatic Brain Injury Patient Biofluids. J Neurotrauma. 2011:861–870. doi: 10.1089/neu.2010.1564. PubMed DOI PMC

Jessen KR, Thorpe R, Mirsky R. Molecular identity, distribution and heterogeneity of glial fibrillary acidic protein: an immunoblotting and immunohistochemical study of Schwann cells, satellite cells, enteric glia and astrocytes. J Neurocytol. 1984;13:187–200. doi: 10.1007/BF01148114. PubMed DOI

Tripathi A, Shrinet K, Kumar A. HMGB1 protein as a novel target for cancer. Toxicol Rep. 2019;6:253–261. doi: 10.1016/j.toxrep.2019.03.002. PubMed DOI PMC

Isgrò MA, Bottoni P, Scatena R. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Adv Exp Med Biol. 2015;867:125–143. doi: 10.1007/978-94-017-7215-0_9. PubMed DOI

Zaheer S, Beg M, Rizvi I, Islam N, Ullah E, Akhtar N. Correlation between serum neuron-specific enolase and functional neurological outcome in patients of acute ischemic stroke. Ann Indian Acad Neurol. 2013;16:504–508. doi: 10.4103/0972-2327.120442. PubMed DOI PMC

Brea D, Sobrino T, Blanco M, Cristobo I, Rodríguez-González R, Rodríguez-Yañez M, Moldes O, et al. Temporal profile and clinical significance of serum neuron-specific enolase and S100 in ischemic and hemorrhagic stroke. Clin Chem Lab Med. 2009;47:1513–1518. doi: 10.1515/CCLM.2009.337. PubMed DOI

Savola O, Pyhtinen J, Leino TK, Siitonen S, Niemela O, Hillbom M. Effects of head and extracranial injuries on serum protein S100B levels in trauma patients. J Trauma. 2004;56:1229–1234. doi: 10.1097/01.TA.0000096644.08735.72. PubMed DOI

Ercole A, Thelin EP, Holst A, Bellander BM, Nelson DW. Kinetic modelling of serum S100b after traumatic brain injury. BMC Neurol. 2016;16:93. doi: 10.1186/s12883-016-0614-3. PubMed DOI PMC

Zimmer DB, Van Eldik LJ. Tissue distribution of rat S100 alpha and S100 beta and S100-binding proteins. Am J Physiol. 1987;252:C285–C289. doi: 10.1152/ajpcell.1987.252.3.C285. PubMed DOI

Kapural M, Krizanac-Bengez L, Barnett G, Perl J, Masaryk T, Apollo D, Rasmussen P, Mayberg MR, Janigro D. Serum S-100beta as a possible marker of blood-brain barrier disruption. Brain Res. 2002;940:102–104. doi: 10.1016/S0006-8993(02)02586-6. PubMed DOI

Michetti F, D'Ambrosi N, Toesca A, Puglisi MA, Serrano A, Marchese E, Corvino V, Geloso MC. The S100B story: from biomarker to active factor in neural injury. J Neurochem. 2019;148:168–187. doi: 10.1111/jnc.14574. PubMed DOI

Anderson RE, Hansson LO, Nilsson O, Dijlai-Merzoug R, Settergren G. High serum S100B levels for trauma patients without head injuries. Neurosurgery. 2001;48:1255–1258. doi: 10.1227/00006123-200106000-00012. Discussion 1258–1260. PubMed DOI

da Rocha AB, Schneider RF, de Freitas GR, André C, Grivicich I, Zanoni C, Fossá A, et al. Role of serum S100B as a predictive marker of fatal outcome following isolated severe head injury or multitrauma in males. Clin Chem Lab Med. 2006;44:1234–1242. doi: 10.1515/CCLM.2006.218. PubMed DOI

Calcagnile O, Anell A, Undén J. The addition of S100B to guidelines for management of mild head injury is potentially cost saving. BMC Neurol. 2016;16:200. doi: 10.1186/s12883-016-0723-z. PubMed DOI PMC

Bheda A, Gullapalli A, Caplow M, Pagano JS, Shackelford J. Ubiquitin editing enzyme UCH L1 and microtubule dynamics: implication in mitosis. Cell Cycle. 2010;9:980–994. doi: 10.4161/cc.9.5.10934. PubMed DOI PMC

Bishop P, Rocca D, Henley JM. Ubiquitin C-terminal hydrolase L1 (UCH-L1): structure, distribution and roles in brain function and dysfunction. Biochem J. 2016;473:2453–2462. doi: 10.1042/BCJ20160082. PubMed DOI PMC

Papa L, Ladde JG, O'Brien JF, Thundiyil JG, Tesar J, Leech S, Cassidy DD, et al. Evaluation of glial and neuronal blood biomarkers compared with clinical decision rules in assessing the need for computed tomography in patients with mild traumatic brain injury. JAMA Netw Open. 2022;5:e221302. doi: 10.1001/jamanetworkopen.2022.1302. PubMed DOI PMC

Wang KK, Yang Z, Zhu T, Shi Y, Rubenstein R, Tyndall JA, Manley GT. An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn. 2018;18:165–180. doi: 10.1080/14737159.2018.1428089. PubMed DOI PMC

Abdelhak A, Foschi M, Abu-Rumeileh S, Yue JK, D'Anna L, Huss A, Oeckl P, et al. Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nat Rev Neurol. 2022;18:158–172. doi: 10.1038/s41582-021-00616-3. PubMed DOI

Thelin EP, Zeiler FA, Ercole A, Mondello S, Büki A, Bellander B-M, Helmy A, et al. Serial sampling of serum protein biomarkers for monitoring human traumatic brain injury dynamics: A systematic review. Front Neurol. 2017;8:300. doi: 10.3389/fneur.2017.00300. PubMed DOI PMC

Chen R, Kang R, Tang D. The mechanism of HMGB1 secretion and release. Exp Mol Med. 2022;54:91–102. doi: 10.1038/s12276-022-00736-w. PubMed DOI PMC

Mo J, Hu J, Cheng X. The role of high mobility group box 1 in neuroinflammatory related diseases. Biomed Pharmacother. 2023;161:114541. doi: 10.1016/j.biopha.2023.114541. PubMed DOI

Gougeon ML, Bras M. Natural killer cells, dendritic cells, and the alarmin high-mobility group box1 protein: a dangerous trio in HIV-1 infection? Curr Opin HIV AIDS. 2011;6:364–372. doi: 10.1097/COH.0b013e328349b089. PubMed DOI

Kwak MS, Kim HS, Lee B, Kim YH, Son M, Shin JS. Immunological Significance of HMGB1 Post-Translational Modification and Redox Biology. Front Immunol. 2020;11:1189. doi: 10.3389/fimmu.2020.01189. PubMed DOI PMC

Peltz ED, Moore EE, Eckels PC, Damle SS, Tsuruta Y, Johnson JL, Sauaia A, Silliman CC, Banerjee A, Abraham E. HMGB1 is markedly elevated within 6 hours of mechanical trauma in humans. Shock. 2009;32:17–22. doi: 10.1097/SHK.0b013e3181997173. PubMed DOI PMC

Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999;285:248–251. doi: 10.1126/science.285.5425.248. PubMed DOI

Zandarashvili L, Sahu D, Lee K, Lee YS, Singh P, Rajarathnam K, Iwahara J. Real-time kinetics of high-mobility group box 1 (HMGB1) oxidation in extracellular fluids studied by in situ protein NMR spectroscopy. J Biol Chem. 2013;288:11621–11627. doi: 10.1074/jbc.M113.449942. PubMed DOI PMC

Evran S, Calis F, Akkaya E, Baran O, Cevik S, Katar S, Gurevin EG, et al. The effect of high mobility group box-1 protein on cerebral edema, blood-brain barrier, oxidative stress and apoptosis in an experimental traumatic brain injury model. Brain Res Bull. 2020;154:68–80. doi: 10.1016/j.brainresbull.2019.10.013. PubMed DOI

Walker LE, Frigerio F, Ravizza T, Ricci E, Tse K, Jenkins RE, Sills GJ, et al. Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy. J Clin Invest. 2019;129:2166. doi: 10.1172/JCI129285. PubMed DOI PMC

Kamaşak T, Dilber B, Yaman SÖ, Durgut BD, Kurt T, Çoban E, Arslan EA, et al. HMGB-1, TLR4, IL-1R1, TNF-α, and IL-1β: novel epilepsy markers? Epileptic Disord. 2020;22:183–193. doi: 10.1684/epd.2020.1155. PubMed DOI

Zhu M, Chen J, Guo H, Ding L, Zhang Y, Xu Y. High Mobility Group Protein B1 (HMGB1) and Interleukin-1β as Prognostic Biomarkers of Epilepsy in Children. J Child Neurol. 2018;33:909–917. doi: 10.1177/0883073818801654. PubMed DOI

Gyorgy A, Ling G, Wingo D, Walker J, Tong L, Parks S, Januszkiewicz A, Baumann R, Agoston DV. Time-dependent changes in serum biomarker levels after blast traumatic brain injury. J Neurotrauma. 2011;28:1121–1126. doi: 10.1089/neu.2010.1561. PubMed DOI

Townend W, Dibble C, Abid K, Vail A, Sherwood R, Lecky F. Rapid elimination of protein S-100B from serum after minor head trauma. J Neurotrauma. 2006;23:149–155. doi: 10.1089/neu.2006.23.149. PubMed DOI

Rech TH, Vieira SR, Nagel F, Brauner JS, Scalco R. Serum neuron-specific enolase as early predictor of outcome after in-hospital cardiac arrest: a cohort study. Crit Care. 2006;10:R133. doi: 10.1186/cc5046. PubMed DOI PMC

Papa L, Brophy GM, Welch RD, Lewis LM, Braga CF, Tan CN, Ameli NJ, et al. Time Course and Diagnostic Accuracy of Glial and Neuronal Blood Biomarkers GFAP and UCH-L1 in a Large Cohort of Trauma Patients With and Without Mild Traumatic Brain Injury. JAMA Neurol. 2016;73:551–560. doi: 10.1001/jamaneurol.2016.0039. PubMed DOI PMC

Plog BA, Dashnaw ML, Hitomi E, Peng W, Liao Y, Lou N, Deane R, Nedergaard M. Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system. J Neurosci. 2015;35:518–526. doi: 10.1523/JNEUROSCI.3742-14.2015. PubMed DOI PMC

Kapural M, Krizanac-Bengez LJ, Barnett G, Perl J, Masaryk T, Apollo D, Rasmussen P, Mayberg MR, Janigro D. Serum S-100beta as a possible marker of blood-brain barrier disruption. Brain Res. 2002;940:102–104. doi: 10.1016/S0006-8993(02)02586-6. PubMed DOI

Undén J, Ingebrigtsen T, Romner B Scandinavian Neurotrauma Committee (SNC) Scandinavian guidelines for initial management of minimal, mild and moderate head injuries in adults: an evidence and consensus-based update. BMC Med. 2013;11:50. doi: 10.1186/1741-7015-11-50. PubMed DOI PMC

Bouvier D, Balayssac D, Durif J, Mourgues C, Sarret C, Pereira B, Sapin V. Assessment of the advantage of the serum S100B protein biomonitoring in the management of pediatric mild traumatic brain injury-PROS100B: protocol of a multicentre unblinded stepped wedge cluster randomized trial. BMJ Open. 2019;9:e027365. doi: 10.1136/bmjopen-2018-027365. PubMed DOI PMC

Go H, Saito Y, Maeda H, Maeda R, Yaginuma K, Ogasawara K, Kashiwabara N, Kawasaki Y, Hosoya M. Serum cytokine profiling in neonates with hypoxic ischemic encephalopathy. J Neonatal Perinatal Med. 2021;14:177–182. doi: 10.3233/NPM-200431. PubMed DOI

Chalak LF, Sánchez PJ, Adams-Huet B, Laptook AR, Heyne RJ, Rosenfeld CR. Biomarkers for severity of neonatal hypoxic-ischemic encephalopathy and outcomes in newborns receiving hypothermia therapy. J Pediatr. 2014;164:468–74.e1. doi: 10.1016/j.jpeds.2013.10.067. PubMed DOI PMC

Douglas-Escobar MV, Heaton SC, Bennett J, Young LJ, Glushakova O, Xu X, Barbeau DY, et al. UCH-L1 and GFAP Serum Levels in Neonates with Hypoxic-Ischemic Encephalopathy: A Single Center Pilot Study. Front Neurol. 2014;5:273. doi: 10.3389/fneur.2014.00273. PubMed DOI PMC

Zaigham M, Lundberg F, Olofsson P. Protein S100B in umbilical cord blood as a potential biomarker of hypoxic-ischemic encephalopathy in asphyxiated newborns. Early Hum Dev. 2017;112:48–53. doi: 10.1016/j.earlhumdev.2017.07.015. PubMed DOI

Zaigham M, Lundberg F, Hayes R, Undén J, Olofsson P. Umbilical cord blood concentrations of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) in neonates developing hypoxic-ischemic encephalopathy. J Matern Fetal Neonatal Med. 2016;29:1822–1828. doi: 10.3109/14767058.2015.1064108. PubMed DOI

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