Journal of Pediatric Biochemistry 2016; 06(02): 88-91
DOI: 10.1055/s-0036-1593755
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Neonatal Brain Hemorrhage: The Role of NonProtein-Bound Iron

Serafina Perrone
1   Department of Molecular and Developmental Medicine, General Hospital “Santa Maria alle Scotte,” University of Siena, Siena, Italy
,
Simona Negro
1   Department of Molecular and Developmental Medicine, General Hospital “Santa Maria alle Scotte,” University of Siena, Siena, Italy
,
Maria Luisa Tataranno
2   Department of Neonatology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands
,
Antonino Santacroce
1   Department of Molecular and Developmental Medicine, General Hospital “Santa Maria alle Scotte,” University of Siena, Siena, Italy
,
Carlotta Bracciali
1   Department of Molecular and Developmental Medicine, General Hospital “Santa Maria alle Scotte,” University of Siena, Siena, Italy
,
Mariangela Longini
1   Department of Molecular and Developmental Medicine, General Hospital “Santa Maria alle Scotte,” University of Siena, Siena, Italy
3   Clinical Pathology, AOUS Siena, Italy
,
Fabrizio Proietti
1   Department of Molecular and Developmental Medicine, General Hospital “Santa Maria alle Scotte,” University of Siena, Siena, Italy
,
Francesco Bazzini
1   Department of Molecular and Developmental Medicine, General Hospital “Santa Maria alle Scotte,” University of Siena, Siena, Italy
,
Elisa Belvisi
1   Department of Molecular and Developmental Medicine, General Hospital “Santa Maria alle Scotte,” University of Siena, Siena, Italy
,
Giuseppe Buonocore
1   Department of Molecular and Developmental Medicine, General Hospital “Santa Maria alle Scotte,” University of Siena, Siena, Italy
,
on behalf of the “Gruppo di Studio di Biochimica Clinica Neonatale della Società Italiana di Neonatologia” › Author Affiliations
Further Information

Publication History

12 July 2016

26 July 2016

Publication Date:
21 October 2016 (online)

Abstract

Intraventricular hemorrhage (IVH) in very preterm infants is a common disease, which can induce long-term consequences. Oxidative stress (OS) occurs easily in preterm newborns due to an imbalance between high free radical (FR) production and the low antioxidant shield, not completely developed at birth. Nonprotein-bound iron (NPBI) concentration in cord blood has been found to be highly predictive for the risk of poor neurodevelopmental outcome. However, at present, no data exist about the exact mechanisms associated with IVH induced by iron-mediated FRs. We propose the hypothesis that hypoxia or ischemia-induced releasing of NPBI is a key regulating event that initiates a vicious circle of excessive FR generation, which in turn participates in edema development, inflammatory reaction, and endothelial injury. This suggests that developing effective neuroprotective strategies for preterm infants requires a detailed understanding of OS reactions and glial responses.

 
  • References

  • 1 McCrea HJ, Ment LR. The diagnosis, management, and postnatal prevention of intraventricular hemorrhage in the preterm neonate. Clin Perinatol 2008; 35 (4) 777-792, vii
  • 2 Perrone S, Tataranno ML, Negro S , et al. Early identification of the risk for free radical-related diseases in preterm newborns. Early Hum Dev 2010; 86 (4) 241-244
  • 3 Colton CA, Gilbert DL. Microglia, an in vivo source of reactive oxygen species in the brain. Adv Neurol 1993; 59: 321-326
  • 4 Inder T, Mocatta T, Darlow B, Spencer C, Volpe JJ, Winterbourn C. Elevated free radical products in the cerebrospinal fluid of VLBW infants with cerebral white matter injury. Pediatr Res 2002; 52 (2) 213-218
  • 5 Saugstad OD. Mechanisms of tissue injury by oxygen radicals: implications for neonatal disease. Acta Paediatr 1996; 85 (1) 1-4
  • 6 McQuillen PS, Ferriero DM. Selective vulnerability in the developing central nervous system. Pediatr Neurol 2004; 30 (4) 227-235
  • 7 Buonocore G, Perrone S, Tataranno ML. Oxygen toxicity: chemistry and biology of reactive oxygen species. Semin Fetal Neonatal Med 2010; 15 (4) 186-190
  • 8 Perrone S, Negro S, Tataranno ML, Buonocore G. Oxidative stress and antioxidant strategies in newborns. J Matern Fetal Neonatal Med 2010; 23 (3) (Suppl. 03) 63-65
  • 9 Longini M, Perrone S, Kenanidis A , et al. Isoprostanes in amniotic fluid: a predictive marker for fetal growth restriction in pregnancy. Free Radic Biol Med 2005; 38 (11) 1537-1541
  • 10 Perrone S, Vezzosi P, Longini M , et al. Biomarkers of oxidative stress in babies at high risk for retinopathy of prematurity. Front Biosci (Elite Ed) 2009; 1 (1) 547-552
  • 11 Perrone S, Tataranno ML, Buonocore G. Oxidative stress and bronchopulmonary dysplasia. J Clin Neonatol 2012; 1 (3) 109-114
  • 12 Buonocore G, Perrone S, Longini M , et al. Non protein bound iron as early predictive marker of neonatal brain damage. Brain 2003; 126 (Pt 5): 1224-1230
  • 13 Hershko C, Peto TEA. Non-transferrin plasma iron. Br J Haematol 1987; 66 (2) 149-151
  • 14 Signorini C, Ciccoli L, Leoncini S , et al. Free iron, total F-isoprostanes and total F-neuroprostanes in a model of neonatal hypoxic-ischemic encephalopathy: neuroprotective effect of melatonin. J Pineal Res 2009; 46 (2) 148-154
  • 15 Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000; 87 (10) 840-844
  • 16 Burkitt MJ, Mason RP. Direct evidence for in vivo hydroxyl-radical generation in experimental iron overload: an ESR spin-trapping investigation. Proc Natl Acad Sci U S A 1991; 88 (19) 8440-8444
  • 17 McCord JM. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 1985; 312 (3) 159-163
  • 18 Halliwell B. The wanderings of a free radical. Free Radic Biol Med 2009; 46 (5) 531-542
  • 19 Buonocore G, Zani S, Perrone S, Caciotti B, Bracci R. Intraerythrocyte nonprotein-bound iron and plasma malondialdehyde in the hypoxic newborn. Free Radic Biol Med 1998; 25 (7) 766-770
  • 20 Ciccoli L, Rossi V, Leoncini S , et al. Iron release, superoxide production and binding of autologous IgG to band 3 dimers in newborn and adult erythrocytes exposed to hypoxia and hypoxia-reoxygenation. Biochim Biophys Acta 2004; 1672 (3) 203-213
  • 21 Wagner KR, Hua Y, de Courten-Myers GM , et al. Tin-mesoporphyrin, a potent heme oxygenase inhibitor, for treatment of intracerebral hemorrhage: in vivo and in vitro studies. Cell Mol Biol 2000; 46 (3) 597-608
  • 22 Xi G, Keep RF, Hoff JT. Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats. J Neurosurg 1998; 89 (6) 991-996
  • 23 Hua Y, Xi G, Keep RF, Hoff JT. Complement activation in the brain after experimental intracerebral hemorrhage. J Neurosurg 2000; 92 (6) 1016-1022
  • 24 Chen Z, Gao C, Hua Y, Keep RF, Muraszko K, Xi G. Role of iron in brain injury after intraventricular hemorrhage. Stroke 2011; 42 (2) 465-470
  • 25 Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39 (1) 44-84
  • 26 Wolin MS, Burke-Wolin TM, Mohazzab-H KM. Roles for NAD(P)H oxidases and reactive oxygen species in vascular oxygen sensing mechanisms. Respir Physiol 1999; 115 (2) 229-238
  • 27 Pae HO, Kim EC, Chung HT. Integrative survival response evoked by heme oxygenase-1 and heme metabolites. J Clin Biochem Nutr 2008; 42 (3) 197-203
  • 28 Thorup C, Jones CL, Gross SS, Moore LC, Goligorsky MS. Carbon monoxide induces vasodilation and nitric oxide release but suppresses endothelial NOS. Am J Physiol 1999; 277 (6 Pt 2): F882-F889
  • 29 Lee PJ, Jiang BH, Chin BY , et al. Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J Biol Chem 1997; 272 (9) 5375-5381
  • 30 Gazzolo D, Perrone S, Paffetti P , et al. Non protein bound iron concentrations in amniotic fluid. Clin Biochem 2005; 38 (7) 674-677
  • 31 Gaasch JA, Lockman PR, Geldenhuys WJ, Allen DD, Van der Schyf CJ. Brain iron toxicity: differential responses of astrocytes, neurons, and endothelial cells. Neurochem Res 2007; 32 (7) 1196-1208
  • 32 Won SM, Lee JH, Park UJ, Gwag J, Gwag BJ, Lee YB. Iron mediates endothelial cell damage and blood–brain barrier opening in the hippocampus after transient forebrain ischemia in rats. Exp Mol Med 2011; 43 (2) 121-128
  • 33 Yang Y, Loscalzo J. Regulation of tissue factor expression in human microvascular endothelial cells by nitric oxide. Circulation 2000; 101 (18) 2144-2148
  • 34 Kartikasari AE, Georgiou NA, Visseren FL, van Kats-Renaud H, van Asbeck BS, Marx JJ. Endothelial activation and induction of monocyte adhesion by nontransferrin-bound iron present in human sera. FASEB J 2006; 20 (2) 353-355
  • 35 Rooyakkers TM, Stroes ES, Kooistra MP , et al. Ferric saccharate induces oxygen radical stress and endothelial dysfunction in vivo. Eur J Clin Invest 2002; 32 (Suppl. 01) 9-16
  • 36 Hawkins BT, Davis TP. The blood–brain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005; 57 (2) 173-185
  • 37 Pomfy M, Húska J. The state of the microcirculatory bed after total ischaemia of the brain. An experimental ultrastructural study. Funct Dev Morphol 1992; 2 (4) 253-258