The Journal of Pediatrics
Volume 153, Issue 2 , Pages 160-163 , August 2008

Postnatal Sepsis, Necrotizing Entercolitis, and the Critical Role of Systemic Inflammation in White Matter Injury in Premature Infants

  • Joseph J. Volpe, MD

      Affiliations

    • Corresponding Author InformationReprint requests: Joseph J. Volpe, MD, Department of Neurology, Children's Hospital Boston, 333 Longwood Ave, Suite 228, Boston, MA 02115.

References 

  1. Volpe JJ. Neurology of the Newborn. 5th edition. Philadelphia: Elsevier; 2008;
  2. Pierson CR, Folkerth RD, Billards SS, Trachtenberg FL, Drinkwater ME, Volpe JJ, et al. Gray matter injury associated with periventricular leukomalacia in the premature infant. Acta Neuropathol. 2007;114:619–631
  3. Shah DK, Doyle LW, Anderson PJ, Bear M, Daley AJ, Hunt RW, et al. Adverse neurodevelopment in preterm infants with postnatal sepsis or necrotizing enterocolitis is mediated by white matter abnormality on magnetic resonance imaging at term. J Pediatr. 2008;153:170–175
  4. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002;110:285–291
  5. Bizzarro MJ, Raskind C, Baltimore RS, Gallagher PG. Seventy-five years of neonatal sepsis at Yale, 1928-2003. Pediatrics. 2005;116:595–602
  6. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. Changes in pathogens causing early-onset sepsis in very low birth weight infants. N Engl J Med. 2002;347:240–247
  7. Makhoul IR, Sujov P, Smolkin T, Lusky A, Reichman B. Pathogen-specific early mortality in very low birth weight infants with late-onset sepsis: a national survey. Clin Infect Dis. 2005;40:218–224
  8. Adams-Chapman I, Stoll BJ. Neonatal infection and long-term neurodevelopmental outcome in the preterm infant. Curr Opin Infect Dis. 2006;19:290–297
  9. Hintz SR, Kendrick DE, Stoll BJ, Vohr BR, Fanaroff AA, Donovan EF, et al. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics. 2005;115:696–703
  10. Salhab WA, Perlman JM, Silver L, Broyles RS. Necrotizing enterocolitis and neurodevelopmental outcome in extremely low birth weight infants <1000 g. J Perinatol. 2004;24:534–540
  11. Stoll BJ, Hansen NI, Adams Chapman I, Fanaroff AA, Hintz SR, Vohr B, et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA. 2004;292:2357–2365
  12. Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Eng J Med. 2006;355:685–694
  13. Gilles FH, Leviton A, Dooling EC. The Developing Human Brain: Growth and Epidemiologic Neuropathology. Boston: John Wright; 1983;
  14. Dammann O, Leviton A. Inflammatory brain damage in preterm newborns: dry numbers, wet lab, and causal inferences. Early Hum Dev. 2004;79:1–15
  15. Edwards AD, Tan S. Perinatal infections, prematurity and brain injury. Curr Opin Pediatr. 2006;18:119–124
  16. Khwaja O, Volpe JJ. Pathogenesis of cerebral white matter injury of prematurity. Arch Dis Child Fetal Neonatal Ed. 2008;93:F153–F161
  17. Haynes RL, Abaud O, Li J, Kinney HC, Voklpe JJ, Folkerth RD. Oxidative and nitrative injury in periventricular leukomalacia: a review. Brain Pathol. 2005;15:225–233
  18. Kadhim HJ, Tabarki B, Verellen G, De Prez C, Rona AM, Sebire G. Inflammatory cytokines in the pathogenesis of periventricular leukomalacia. Neurology. 2001;56:1278–1284
  19. Matute C, Alberdi E, Domercq M, Sanchez-Gomez MV, Perez-Samartin A, Rodriguez-Antiguedad A, et al. Excitotoxic damage to white matter. J Anat. 2007;210:693–702
  20. Billiards SS, Haynes RL, Folkerth RD, Trachtenberg FL, Liu LG, Volpe JJ, et al. Development of microglia in the cerebral white matter of the human fetus and infant. J Comp Neurol. 2006;497:199–208
  21. Soul JS, Hammer PE, Tsuji M, Saul P, Bassan H, Limperopoulos C, et al. Fluctuating pressure-passivity is common in the cerebral circulation of sick premature infants. Pediatr Res. 2007;61:467–473
  22. Yanowitz TD, Potter DM, Bowen A, Baker RW, Roberts JM. Variability in cerebral oxygen delivery is reduced in premature neonates exposed to chorioamnionitis. Pediatr Res. 2006;59:299–304
  23. Sharma R, Tepas JJ, Hudak ML, Mollitt DL, Wludyka PS, Teng RJ, et al. Neonatal gut barrier and multiple organ failure: role of endotoxin and proinflammatory cytokines in sepsis and necrotizing enterocolitis. J Pediatr Surg. 2007;42:454–461
  24. Eklind S, Mallard C, Leverin AL, Gilland E, Blomgren K, Mattsby-Baltzer I, et al. Bacterial endotoxin sensitizes the immature brain to hypoxic-ischaemic injury. Eur J Neurosci. 2001;13:1101–1106
  25. Lehnardt S, Massillon L, Follet P, Jensen FE, Ratan RR, Rosenberg PA, et al. Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4–dependent pathway. Proc Natl Acad Sci U S A. 2003;8514–8519
  26. Ikeda T, Mishima K, Aoo N, Egashira N, Iwasaki K, Fujiwara M, et al. Combination treatment of neonatal rats with hypoxia-ischemia and endotoxin induces long-lasting memory and learning impairment that is associated with extended cerebral damage. Am J Obstet Gynecol. 2004;191:2132–2141
  27. Larouche A, Roy M, Kadhim H, Tsanaclis AM, Fortin D, Sebire G. Neuronal injuries induced by perinatal hypoxic-ischemic insults are potentiated by prenatal exposure to lipopolysaccharide: animal model for perinatally acquired encephalopathy. Dev Neurosci. 2005;27:134–142
  28. Wang X, Hagberg H, Nie C, Zhu C, Ikeda T, Mallard C. Dual role of intrauterine immune challenge on neonatal and adult brain vulnerability to hypoxia-ischemia. J Neuropathol Exp Neurol. 2007;66:552–561
  29. Eklind S, Hagberg H, Wang X, Savman K, Leverin AL, Hedtjarn M, et al. Effect of lipopolysaccharide on global gene expression in the immature rat brain. Pediatr Res. 2006;60:161–168
  30. Hagberg H, Mallard C. Effect of inflammation on central nervous system development and vulnerability. Curr Opin Neurol. 2005;18:117–123
  31. Fleer A, Krediet TG. Innate immunity: Toll-like receptors and some more (A brief history, basic organization and relevance for the human newborn). Neonatology. 2007;92:145–157
  32. Lehnardt S, Lachance C, Patrizi S, Lefebvre S, Follett PL, Jensen FE, et al. The Toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS. J Neurosci. 2002;22:2478–2486
  33. Lehnardt S, Henneke P, Lien E, Kasper DL, Volpe JJ, Bechmann I, et al. A mechanism for neurodegeneration induced by group B streptococci through activation of the TLR2/MyD88 pathway in microglia. J Immunol. 2006;177:583–592
  34. Hoffmann O, Braun JS, Becker D, Halle A, Freyer D, Dagand E, et al. TLR2 mediates neuroinflammation and neuronal damage. J Immunol. 2007;178:6476–6481
  35. Pachter JS, De Vries HE, Fabry Z. The blood-brain barrier and its role in immune privilege in the central nervous system. J Neuropath Exp Neurol. 2003;62:593–604
  36. Chakravarty S, Herkenham M. Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines. J Neurosci. 2005;25:1788–1796
  37. Stolp HB, Ek CJ, Johansson PA, Dziegielewska KM, Potter AM, Habgood MD, et al. Effect of minocycline on inflammation-induced damage to the blood-brain barrier and white matter during development. Eur J Neurosci. 2007;26:3465–3474
  38. Miyake K. Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol. 2007;19:3–10
  39. Tang SC, Arumugam TV, Xu X, Cheng A, Mughal MR, Jo DG, et al. Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proc Natl Acad Sci U S A. 2007;104:13798–13803
  40. Lehnardt S, Lehmann S, Kaul D, Tschimmel K, Hoffmann O, Cho S, et al. Toll-like receptor 2 mediates CNS injury in focal cerebral ischemia. J Neuroimmunol. 2007;190:28–33

PII: S0022-3476(08)00332-6

doi: 10.1016/j.jpeds.2008.04.057

The Journal of Pediatrics
Volume 153, Issue 2 , Pages 160-163 , August 2008

Article Tools