Abstract：Objective To study the clinical value of serum neuroglobin in evaluating hypoglycemic brain injury in neonates. Methods A total of 100 neonates with hypoglycemia were enrolled as subjects. According to amplitude-integrated EEG (aEEG) findings and/or clinical manifestations, they were divided into symptomatic hypoglycemic brain injury group (n=22), asymptomatic hypoglycemic brain injury group (n=37) and hypoglycemic non-brain injury group (n=41). The three groups were compared in terms of blood glucose, duration of hypoglycemia, levels of neuroglobin and neuron-specific enolase (NSE), and modified aEEG score. The correlation of neuroglobin with NSE and modified aEEG score was analyzed. The receiver operating characteristic (ROC) curve was plotted. Results Compared with the asymptomatic hypoglycemic brain injury and hypoglycemic non-brain injury groups, the symptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia (P < 0.05). Compared with the hypoglycemic non-brain injury group, the asymptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia (P < 0.05). Neuroglobin was positively correlated with NSE and duration of hypoglycemia (r=0.922 and 0.929 respectively; P < 0.05) and negatively correlated with blood glucose and modified aEEG score (r=-0.849 and -0.968 respectively; P < 0.05). The areas under the ROC curve of neuroglobin, NSE and modified aEEG score were 0.894, 0.890 and 0.941 respectively, and neuroglobin had a sensitivity of 80.8% and a specificity of 95.8% at the optimal cut-off value of 108 mg/L. Conclusions Like NSE and modified aEEG score, serum neuroglobin can also be used as a specific indicator for the assessment of brain injury in neonates with hypoglycemia and has a certain value in clinical practice.
JIANG Feng-Yuan,LIU Hui-Ping,CHEN Li-Ting et al. Clinical value of serum neuroglobin in evaluating hypoglycemic brain injury in neonates[J]. CJCP, 2019, 21(6): 573-579.
Chau V, Poskitt KJ, Sargent MA, et al. Comparison of computer tomography and magnetic resonance imaging scans on the third day of life in term newborns with neonatal encephalopathy[J]. Pediatrics, 2009, 123(1):319-326.
[2]
Burmester T, Weich B, Reinhardt S, et al. A vertebrate globin expressed in the brain[J]. Nature, 2000, 407(6803):520-523.
[3]
Zhang LN, Ai YH, Gong H, et al. Expression and role of neuroglobin in rats with sepsis-associated encephalopathy[J]. Crit Care Med, 2014, 42(1):e12-e21.
Burdjalov VF, Baumgart S, Spitzer AR. Cerebral function monitoring:a new scoring system for the evaluation of brain maturation in neonates[J]. Pediatrics, 2003, 112(4):855-861.
Stanley CA, Rozance PJ, Thornton PS, et al. Re-evaluating "transitional neonatal hypoglycemia":mechanism and implications for management[J]. J Pediar, 2015, 166(6):1520-1525.e1.
[11]
Harris DL, Weston PJ, Harding JE. Incidence of neonatal hypoglcemia in babies identified as at risk[J]. J Pediatr, 2012, 161(5):787-791.
Jain A, Aggarwal R, Jeeva Sankar M, et al. Hypoglycemia in the newborn[J]. Indian J Pediatr, 2010, 77(10):1137-1142.
[14]
Harris DL, Weston PJ, Harding JE. Lactate, rather than ketones, may provide alternative cerebral fuel in hypoglycaemic newborns[J]. Arch Dis Child Fetal Neonatal Ed, 2015, 100(2):F161-F164.
Arhan E, Öztürk Z, Serdaroğlu A, et al. Neonatal hypoglycemia:a wide range of electroclinical manifestations and seizure outcomes[J]. Eur J Paediatr Neurol, 2017, 21(5):738-744.
[17]
Styne DM, Arslanian SA, Connor EL, et al. Pediatric obesity - assessment, treatment and prevention:an Endocrine Society clinical practice guideline[J]. J Clin Endotrinol Metab, 2017, 102(3):709-757.
[18]
Wong DS, Poskitt KJ, Chau V, et al. Brain injury patterns in hypoglycemia in neonatal encephalopathy[J]. AJNR Am J Neuroradiol, 2013, 34(7):1456-1461.
[19]
Bonifacio SL, Glass HC, Peloquin S, et al. A new neurological focus in neonatal intensive care[J]. Nat Rev Neurol, 2011, 7(9):485-494.
Brandner S, Thaler C, Buchfelder M, et al. Brain-derived protein concentrations in the cerebrospinal fluid:contribution of trauma resulting from ventricular drain insertion[J]. J Neurotrauma, 2013, 30(13):1205-1210.
[23]
Haque A, Polcyn R, Matzelle D, et al. New insights into the role of neuron-specific enolase in neuro-inflammation, neurodegeneration, and neuroprotection[J]. Brain Sci, 2018, 8(2). pii:E33.
Boron I, Capece L, Pennacchietti F, et al. Engineered chimeras reveal the structural basis of hexacoordination in globins:a case study of neuroglobin and myoglobin[J]. Biochim Biophys Acta, 2015, 1850(1):169-177.
[27]
Garofalo T, Ferri A, Sorice M, et al. Neuroglobin overexpression plays a pivotal role in neuroprotection through mitochondrial raft-like microdomains in neuroblastoma SK-N-BE2 cells[J]. Mol Cell Neurosci, 2018, 88:167-176.
Wakasugi K, Nakano T, Morishima I. Oxidized human neuroglobin acts as a heterotrimeric Gα protein guanine nucleotide dissociation inhibitor[J]. J Biol Chem, 2003, 278(38):36505-36512.
