While the survival rate of preterm infants has continually increased with the development of perinatal and neonatal monitoring techniques, the incidence of brain injury in preterm infants has been increasing, resulting in varying degrees of cognitive impairment and movement disorders. Measuring the biomarkers of brain damage is an important means to diagnose brain injury. The biomarkers can be divided into neuroglial damage markers, neuronal damage markers and other markers according to the features of injured cells. The biomarkers widely used in clinical practice include S100B protein, myelin basic protein and neuron-specific enolase. Recent studies have newly discovered a collection of markers that can suggest potential brain injury in preterm infants, such as glial fibrillary acidic protein, neurofilament light chain protein, α-II spectrin breakdown products, chemokines, melatonin and urinary metabolomics. These biomarkers can contribute to the early diagnosis and treatment of preterm brain injury, essential for improving neural development and prognosis. This article reviews the latest research advances in the biomarkers of preterm brain injury, in order to provide evidence for the early diagnosis and treatment of this condition.
YAO Mei, MAO Shan-Shan.
Research advances in the biomarkers of brain damage in preterm infants[J]. Chinese Journal of Contemporary Pediatrics. 2019, 21(11): 1138-1143 https://doi.org/10.7499/j.issn.1008-8830.2019.11.015
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参考文献
[1] Galinsky R, Lear CA, Dean JM, et al. Complex interactions between hypoxia-ischemia and inflammation in preterm brain injury[J]. Dev Med Child Neurol, 2018, 60(2):126-133. [2] Ma L, Li Y, Wang J, et al. Quality of life is related to social support in elderly osteoporosis patients in a Chinese population[J]. PLoS One, 2015, 10(6):e0127849. [3] Leviton A, Allred EN, Fichorova RN, et al. Circulating biomarkers in extremely preterm infants associated with ultrasound indicators of brain damage[J]. Eur J Paediatr Neurol, 2018, 22(3):440-450. [4] Massaro AN, Wu YW, Bammler TK, et al. Plasma biomarkers of brain injury in neonatal hypoxic-ischemic encephalopathy[J]. J Pediatr, 2018, 194:67-75. [5] Velipaşaoğlu M, Yurdakök M, Özyüncü Ö, et al. Neural injury markers to predict neonatal complications in intrauterine growth restriction[J]. J Obstet Gynaecol, 2015, 35(6):555-560. [6] Sannia A, Risso FM, Zimmermann LJ, et al. S100B urine concentrations in late preterm infants are gestational age and gender dependent[J]. Clin Chim Acta, 2013, 417:31-34. [7] Murabayashi M, Minato M, Okuhata Y, et al. Kinetics of serum S100B in newborns with intracranial lesions[J]. Pediatr Int, 2008, 50(1):17-22. [8] Serpero LD, Pluchinotta F, Gazzolo D. The clinical and diagnostic utility of S100B in preterm newborns[J]. Clin Chim Acta, 2015, 444:193-198. [9] Chaparro-Huerta V, Flores-Soto ME, Merin Sigala ME, et al. Proinflammatory cytokines, enolase and S-100 as early biochemical indicators of hypoxic-ischemic encephalopathy following perinatal asphyxia in newborns[J]. Pediatr Neonatol, 2017, 58(1):70-76. [10] Dimopoulos C, Damaskos C, Papadakis M, et al. Expression of S100B protein in ischemia/reperfusion-induced brain injury after cyclosporine therapy:a biochemical serum marker with prognostic value?[J]. Med Sci Monit, 2019, 25:1637-1644. [11] Luo Q, Pin T, Dai L, et al. The role of S100B protein at 24 hours of postnatal age as early indicator of brain damage and prognostic parameter of perinatal asphyxia[J]. Glob Pediatr Health, 2019, 6:2333794X19833729. [12] Michetti F, D'Ambrosi N, Toesca A, et al. The S100B story:from biomarker to active factor in neural injury[J]. J Neurochem, 2019, 148(2):168-187. [13] Lu H, Huang W, Chen X, et al. Relationship between premature brain injury and multiple biomarkers in cord blood and amniotic fluid[J]. J Matern Fetal Neonatal Med, 2018, 31(21):2898-2904. [14] Rangon CM, Schang AL, Van Steenwinckel J, et al. Myelination induction by a histamine H3 receptor antagonist in a mouse model of preterm white matter injury[J]. Brain Behav Immun, 2018, 74:265-276. [15] Zhou W, Li W, Qu LH, et al. Relationship of plasma S100B and MBP with brain damage in preterm infants[J]. Int J Clin Exp Med, 2015, 8(9):16445-16453. [16] Schiff L, Hadker N, Weiser S, et al. A literature review of the feasibility of glial fibrillary acidic protein as a biomarker for stroke and traumatic brain injury[J]. Mol Diagn Ther, 2012, 16(2):79-92. [17] Stewart A, Tekes A, Huisman TA, et al. Glial fibrillary acidic protein as a biomarker for periventricular white matter injury[J]. Am J Obstet Gynecol, 2013, 209(1):27.e1-e7. [18] Sanches EF, van de Looij Y, Toulotte A, et al. Mild neonatal brain hypoxia-ischemia in very immature rats causes long-term behavioral and cerebellar abnormalities at adulthood[J]. Front Physiol, 2019, 10:634. [19] Douglas-Escobar MV, Heaton SC, Bennett J, et al. UCH-L1 and GFAP serum levels in neonates with hypoxic-ischemic encephalopathy:a single center pilot study[J]. Front Neurol, 2014, 5:273. [20] Cho KHT, Wassink G, Galinsky R, et al. Protective effects of delayed intraventricular TLR7 agonist administration on cerebral white and gray matter following asphyxia in the preterm fetal sheep[J]. Sci Rep, 2019, 9(1):9562. [21] Papa L, Silvestri S, Brophy GM, et al. GFAP out-performs S100β in detecting traumatic intracranial lesions on computed tomography in trauma patients with mild traumatic brain injury and those with extracranial lesions[J]. J Neurotrauma, 2014, 31(22):1815-1822. [22] Paliwal MN, Paliwal P, Varma M, et al. Study of neuron specific enolase (NSE) in perinatal asphyxia & its role as an early marker of brain injury[J]. J Evid Based Med Health, 2016, 3(67):3640-3643. [23] Yuan A, Rao MV, Veeranna, et al. Neurofilaments and neurofilament proteins in health and disease[J]. Cold Spring Harb Perspect Biol, 2017, 9(4). pii:a018309. [24] Toorell H, Zetterberg H, Blennow K, et al. Increase of neuronal injury markers Tau and neurofilament light proteins in umbilical blood after intrapartum asphyxia[J]. J Matern Fetal Neonatal Med, 2018, 31(18):2468-2472. [25] Depoorter A, Neumann RP, Barro C, et al. Neurofilament light chain:blood biomarker of neonatal neuronal injury[J]. Front Neurol, 2018, 9:984. [26] Kuhle J, Barro C, Andreasson U, et al. Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples:ELISA, electrochemiluminescence immunoassay and Simoa[J]. Clin Chem Lab Med, 2016, 54(10):1655-1661. [27] Figueira RL, Gonçalves FL, Simões AL, et al. Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia[J]. Braz J Med Biol Res, 2016, 49(7):e5258. [28] Yan C, Zhang B. Clinical significance of detecting serum melatonin and SBDPs in brain injury in preterm infants[J]. Pediatr Neonatol, 2019, 60(4):435-440. [29] Wu H, Li Z, Yang X, et al. SBDPs and Tau proteins for diagnosis and hypothermia therapy in neonatal hypoxic ischemic encephalopathy[J]. Exp Ther Med, 2017, 13(1):225-229. [30] Pearn ML, Niesman IR, Egawa J, et al. Pathophysiology associated with traumatic brain injury:current treatments and potential novel therapeutics[J]. Cell Mol Neurobiol, 2017, 37(4):571-585. [31] Tenreiro MM, Ferreira R, Bernardino L, et al. Cellular response of the blood-brain barrier to injury:potential biomarkers and therapeutic targets for brain regeneration[J]. Neurobiol Dis, 2016, 91:262-273. [32] Wang LY, Tu YF, Lin YC, et al. CXCL5 signaling is a shared pathway of neuroinflammation and blood-brain barrier injury contributing to white matter injury in the immature brain[J]. J Neuroinflammation, 2016, 13:6. [33] Paton MCB, McDonald CA, Allison BJ, et al. Perinatal brain injury as a consequence of preterm birth and intrauterine inflammation:designing targeted stem cell therapies[J]. Front Neurosci, 2017, 11:200. [34] Marseglia L, D'Angelo G, Manti S, et al. Melatonin secretion is increased in children with severe traumatic brain injury[J]. Int J Mol Sci, 2017, 18(5). pii:E1053. [35] Aly H, Elmahdy H, El-Dib M, et al. Melatonin use for neuroprotection in perinatal asphyxia:a randomized controlled pilot study[J]. J Perinatol, 2015, 35(3):186-191. [36] Lee JY, Song H, Dash O, et al. Administration of melatonin for prevention of preterm birth and fetal brain injury associated with premature birth in a mouse model[J]. Am J Reprod Immunol, 2019, 82(3):e13151. [37] Shah SA, Khan M, Jo MH, et al. Melatonin stimulates the SIRT1/Nrf2 signaling pathway counteracting lipopolysaccharide (LPS)-induced oxidative stress to rescue postnatal rat brain[J]. CNS Neurosci Ther, 2017, 23(1):33-44. [38] Xu W, Lu X, Zheng J, et al. Melatonin protects against neuronal apoptosis via suppression of the ATF6/CHOP pathway in a rat model of intracerebral hemorrhage[J]. Front Neurosci, 2018, 12:638. [39] Tataranno ML, Perrone S, Longini M, et al. Predictive role of urinary metabolic profile for abnormal MRI score in preterm neonates[J]. Dis Markers, 2018, 2018:4938194. [40] An M, Gao Y. Urinary biomarkers of brain diseases[J]. Genomics Proteomics Bioinformatics, 2015, 13(6):345-354. [41] Wu J, Gao Y. Physiological conditions can be reflected in human urine proteome and metabolome[J]. Expert Rev Proteomics, 2015, 12(6):623-636. [42] Sarafidis K, Begou O, Deda O, et al. Targeted urine metabolomics in preterm neonates with intraventricular hemorrhage[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2019, 1104:240-248.
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