Journal Mobile Options
Table of Contents
Vol. 28, No. 4-5, 2006
Issue release date: August 2006
Dev Neurosci 2006;28:244–255

Pediatric Traumatic Brain Injury: Quo Vadis?

Kochanek P.M.
Departments of Critical Care Medicine, Anesthesiology and Pediatrics, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, Pa., USA

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


In this review, five questions serve as the framework to discuss the importance of age-related differences in the pathophysiology and therapy of traumatic brain injury (TBI). The following questions are included: (1) Is diffuse cerebral swelling an important feature of pediatric TBI and what is its etiology? (2) Is the developing brain more vulnerable than the adult brain to apoptotic neuronal death after TBI and, if so, what are the clinical implications? (3) If the developing brain has enhanced plasticity versus the adult brain, why are outcomes so poor in infants and young children with severe TBI? (4) What contributes to the poor outcomes in the special case of inflicted childhood neurotrauma and how do we limit it? (5) Should both therapeutic targets and treatments of pediatric TBI be unique? Strong support is presented for the existence of unique biochemical, molecular, cellular and physiological facets of TBI in infants and children versus adults. Unique therapeutic targets and enhanced therapeutic opportunities, both in the acute phase after injury and in rehabilitation and regeneration, are suggested.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Adelson PD, Bratton SL, Carney NA, Chesnut RM, du Coudray HEM, Goldstein B, Kochanek PM, Miller HC, Partington MD, Selden NR, Warden CR, Wright DW: Guidelines for the acute medical management of severe traumatic brain injury in infants, children and adolescents. Pediatr Crit Care Med Suppl 2003;4:S1–S75.

    External Resources

  2. Reece RM, Nicholson CE: Inflicted Childhood Neurotrauma. The American Academy of Pediatrics, Proceedings of the Inflicted Childhood Neurotrauma Conference, October 10–11, 2002. Bethesda, American Academy of Pediatrics, 2003, pp 1–300.
  3. Kochanek AR, Kline AE, Gao W-M, Chadha M, Lai Y-C, Clark RSB, Dixon CE, Jenkins LW: Gel-based hippocampal proteomic analysis 2 weeks following traumatic brain injury to immature rats using controlled cortical impact. Dev Neurosci 2006;28:410–419.
  4. Kochanek PM, Bell MJ, Forbes ML, Adelson PD, Clark RSB: Pediatric brain injuries: pathophysiology; in Marion DW (ed): Traumatic Brain Injury. New York, Thieme Medical Publishers, 1999, pp 233–256.
  5. Kochanek PM, Clark RSB, Ruppel RA, Adelson PD, Bell MJ, Whalen MJ, Robertson CL, Satchell MA, Seidberg NA, Marion DW, Jenkins LW: Biochemical, cellular and molecular mechanisms in the evolution of secondary damage after severe traumatic brain injury in infants and children: lessons learned from the bedside. Pediatr Crit Care Med 2000;1:4–19.
  6. Hendrick EB, Harwood-Nash DCF, Hudson AR: Head injuries in children: a survey of 4465 consecutive cases at the Hospital for Sick Children, Toronto, Canada. Clin Neurosurg 1964;11:46–65.
  7. Bruce DA, Raphaely RC, Goldberg AI, Zimmerman RA, Bilaniuk LT, Schut L, Kuhl DE: Pathophysiology, treatment and outcome following severe head injury in children. Childs Brain 1979;5:174–191.
  8. Raphaely RC, Swedlow DB, Downes JJ, Bruce DA: Management of severe pediatric head trauma. Pediatr Clin North Am 1980;27:715–727.
  9. Bruce DA, Alavi A, Bilaniuk L, Dolinskas C, Obrist W, Uzzell B: Diffuse cerebral swelling following head injuries in children: the syndrome of ‘malignant brain edema’. J Neurosurg 1981;54:170–178.
  10. Langfitt TW, Kassell NF: Cerebral vasodilatation produced by brain-stem stimulation: neurogenic control vs autoregulation. Am J Physiol 1968;215:90–97.
  11. Muizelaar JP, Marmarou A, DeSalles AA, Ward JD, Zimmerman RS, Li Z, Choi SC, Young HF: Cerebral blood flow and metabolism in severely head-injured children. 1. Relationship with GCS score, outcome, ICP, and PVI. J Neurosurg 1989;71:63–71.
  12. Muizelaar JP, Ward JD, Marmarou A, Newlon PG, Wachi A: Cerebral blood flow and metabolism in severely head-injured children. 2. Autoregulation. J Neurosurg 1989;71:72–76.
  13. Biagas KV, Grundl PD, Kochanek PM, Schiding JK, Nemoto EM: Posttraumatic hyperemia in immature, mature, and aged rats: autoradiographic determination of cerebral blood flow. J Neurotrauma 1996;13:189–200.
  14. Durham SR, Raghupathi R, Helfaer MA, Marwaha S, Duhaime AC: Age-related differences in acute physiologic response to focal traumatic brain injury in piglets. Pediatr Neurosurg 2000;33:76–82.
  15. Sharples PM, Stuart AG, Matthews DS, Aynsley-Green A, Eyre JA: Cerebral blood flow and metabolism in children with severe head injury. 1. Relation to age, Glasgow coma score, outcome, intracranial pressure, and time after injury. J Neurol Neurosurg Psychiatry 1995;58:145–152.
  16. Sharples PM, Matthews DS, Eyre JA: Cerebral blood flow and metabolism in children with severe head injuries. 2. Cerebrovascular resistance and its determinants. J Neurol Neurosurg Psychiatry 1995;58:153–159.
  17. Adelson PD, Clyde B, Kochanek PM, Wisniewski S, Marion DW, Yonas H: Cerebrovascular response in infants and young children following severe traumatic brain injury: a preliminary report. Pediatr Neurosurg 1997;26:200–207.
  18. Skippen P, Seear M, Poskitt K, Kestle J, Cochrane D, Annich G, Handel J: Effect of hyperventilation on regional cerebral blood flow in head-injured children. Crit Care Med 1997;25:1402–1409.
  19. Suzuki K: The changes of regional cerebral blood flow with advancing age in normal children. Nagoya Med J 1990;34:159–170.
  20. Zwienenberg M, Muizelaar JP: Severe pediatric head injury: the role of hyperemia revisited. J Neurotrauma 1999;16:937–943.
  21. Lang DA, Teasdale GM, Macpherson P, Lawrence A: Diffuse brain swelling after head injury: more often malignant in adults than children? J Neurosurg 1994;80:675–680.
  22. Aldrich EF, Eisenberg HM, Saydjari C, Luerssen TG, Foulkes MA, Jane JA, Marshall LF, Marmarou A, Young HF: Diffuse brain swelling in severely head-injured children. J Neurosurg 1992;76:450–454.
  23. Margulies SS, Thibault KL: Infant skull and suture properties: measurements and implications for mechanisms of pediatric brain injury. J Biomech Eng 2000;122:364–371.
  24. Grundl PD, Biagas KV, Kochanek PM, Schiding JK, Barmada M, Nemoto EM: Early cerebrovascular response to head injury in immature and mature rats. J Neurotrauma 1994;11:135–148.
  25. Van Lookeren Campagne M, Verheul JB, Nicolay K, Balazs R: Early evolution and recovery from excitotoxic injury in the neonatal rat brain: a study combining magnetic resonance imaging, electrical impedance, and histology. J Cereb Blood Flow Metab 1994;14:1011–1023.
  26. Clark RS, Kochanek PM, Schwarz MA, Schiding JK, Turner DS, Chen M, Carlos TM, Watkins SC: Inducible nitric oxide synthase expression in cerebrovascular smooth muscle and neutrophils after traumatic brain injury in immature rats. Pediatr Res 1996;39:784–790.
  27. Adelson PD, Whalen M, Robichaud P, Carlos T, Kochanek P: Blood brain barrier permeability and acute inflammation in two models of TBI in the immature rat: a preliminary report. Acta Neurochir Suppl 1998;71:104–106.
  28. Schleien CL, Koehler RC, Shaffner DH, Eberle B, Traystman RJ: Blood-brain barrier disruption after cardiopulmonary resuscitation in immature swine. Stroke 1991;22:477–483.
  29. Marmarou A, Fatouros PP, Barzo P, Portella G, Yoshihara M, Tsuji O, Yamamoto T, Laine F, Signoretti S, Ward JD, Bullock MR, Young HF: Contribution of edema and cerebral blood volume to traumatic brain swelling in head-injured patients. J Neurosurg 2001;93:183–193.
  30. Adelson PD, Robichaud P, Hamilton RL, Kochanek PM: A model of diffuse traumatic brain injury in the immature rat. J Neurosurg 1996;85:877–884.
  31. Ito J, Marmarou A, Barzo P, Fatouros P, Corwin F: Characterization of edema by diffusion-weighted imaging in experimental traumatic brain injury. J Neurosurg 1996;84:97–103.
  32. Berger RP, Adelson PD, Richichi R, Kochanek PM: Serum biomarkers after traumatic and hypoxemic brain injuries: insight into the biochemical response of the pediatric brain to inflicted brain injury. Dev Neurosci, submitted.
  33. Raghupathi R, Margulies SS: Traumatic axonal injury after closed head injury in the neonatal pig. J Neurotrauma 2002;19:843–853.
  34. Shaver EG, Duhaime AC, Curtis M, Gennarelli LM, Barrett R: Experimental acute subdural hematoma in infant piglets. Pediatr Neurosurg 1996;25:123–129.
  35. Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K, Tenkova TI, Stefovska V, Turski L, Olney JW: Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 1999;283:70–74.
  36. Pohl D, Bittigau P, Ishimaru MJ, Stadthaus D, Hubner C, Olney JW, Turski L, Ikonomidou C: N-Methyl-D-aspartate antagonists and apoptotic cell death triggered by head-trauma in developing rat brain. Proc Natl Acad Sci USA 1999;96:2508–2513.
  37. Bittigau P, Sifringer M, Pohl D, Stadthaus D, Ishimaru M, Shimizu H, Ikeda M, Lang D, Speer A, Olney JW, Ikonomidou C: Apoptotic neurodegeneration following trauma is markedly enhanced in the immature brain. Ann Neurol 1999;45:724–735.
  38. Bittigau P, Pohl D, Sifringer M, Shimizu H, Ikeda M, Ishimaru M, Stadthaus D, Fuhr S, Dikranian K, Olney JW, Ikonomidou C: Modeling pediatric head trauma: mechanisms of degeneration and potential strategies for neuroprotection. Restor Neurol Neurosci 1998;13:11–23.
  39. Kochanek PM, Clark RSB, Statler KD, Jenkins LW: Physiological assessment and control in studies evaluating CNS injury: should size matter (editorial)? Anesth Analg, in press.
  40. Clark RSB, Kochanek PM, Adelson PD, Bell MJ, Carcillo JA, Chen M, Wisniewski SR, Janesko K, Whalen MJ, Graham SH: Increases in Bcl-2 protein in cerebrospinal fluid and evidence for programmed cell death in infants and children following severe traumatic brain injury. J Pediatr 2000;137:197–204.
  41. Satchell MA, Lai Y, Kochanek PM, Wisniewski SR, Fink EL, Siedberg NA, Berger RP, DeKosky ST, Adelson PD, Clark RSB: Cytochrome c, a biomarker of apoptosis, is increased in cerebrospinal fluid from infants with inflicted brain injury from child abuse. J Cereb Blood Flow Metab 2005;25:919–927.
  42. Berger RP, Janesko KL, Wisniewski SR, Adelson PD, Clark RSB, Ruppel R, Pierce MC, Kochanek PM: Neuron-specific enolase and S100B in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatrics 2002;109:E31.
  43. Robertson CL, Bucci CJ, Fiskum G: Mitochondrial response to calcium in the developing brain. Brain Res Dev Brain Res 2004;151:141–148.
  44. Prins ML, Lee SM, Cheng CL, Becker DP, Hovda DA: Fluid percussion brain injury in the developing and adult rat: a comparative study of mortality, morphology, intracranial pressure and mean arterial blood pressure. Brain Res Dev Brain Res 1996;95:272–282.
  45. Duhaime AC, Margulies SS, Durham SR, O’Rourke MM, Golden JA, Marwaha S, Raghupathi R: Maturation-dependent response of the piglet brain to scaled cortical impact. J Neurosurg 2000;93:455–462.
  46. Levin HS, Aldrich EF, Saydjari C, Eisenberg HM, Foulkes MA, Bellefleur M, Luerssen TG, Jane JA, Marmarou A, Marshall LF, Young HF: Severe head injury in children: experience of the Traumatic Coma Data Bank. Neurosurgery 1992;31:435–443; discussion 443–444.
  47. Kennard MA: Reorganization of motor function in the cerebral cortex of monkeys deprived of motor and premotor areas in infancy. J Neurophysiol 1938;1:477–496.

    External Resources

  48. Villablanca JR, Carlson-Kuhta P, Schmanke TD, Hovda DA: A critical maturational period of reduced brain vulnerability to developmental injury. 1. Behavioral studies in cats. Brain Res Dev Brain Res 1998;105:309–324.
  49. Villablanca JR, Hovda DA: Developmental neuroplasticity in a model of cerebral hemispherectomy and stroke. Neuroscience 2000;95:625–637.
  50. Prins ML, Hovda DA: Developing experimental models to address traumatic brain injury in children. J Neurotrauma 2003;20:123–137.
  51. McDonald JW, Silverstein FS, Johnston MV: Neurotoxicity of N-methyl-D-aspartate is markedly enhanced in developing rat central nervous system. Brain Res 1988;459:200–203.
  52. Kolb B, Tomie JA: Recovery from early cortical damage in rats. 4. Effects of hemidecortication at 1, 5 or 10 days of age on cerebral anatomy and behavior. Behav Brain Res 1988;28:259–274.
  53. Fineman I, Giza CC, Nahed BV, Lee SM, Hovda DA: Inhibition of neocortical plasticity during development by a moderate concussive brain injury. J Neurotrauma 2000;17:739–749.
  54. Giza CC, Maria NS, Hovda DA: N-methyl-D-aspartate receptor subunit changes after traumatic injury to the developing brain. J Neurotrauma 2006;23:950–961.
  55. Barlow KM, Thomson E, Johnson D, Minnus RA: Late neurologic and cognitive sequelae of inflicted traumatic brain injury in infancy. Pediatrics 2005;116:e174–e185.
  56. Hanten G, Bartha M, Levin HS: Metacognition following pediatric traumatic brain injury: a preliminary study. Dev Neuropsychol 2000;18:383–398.
  57. Levin HS, Hanten G, Zhang L, Swank PR, Hunter J: Selective impairment of inhibition after TBI in children. J Clin Exp Neuropsychol 2004;26:589–597.
  58. Tasker RC, Salmond CH, Westland AG, Pena A, Gillard JH, Sahakian BJ, Pickard JD: Head circumference and brain and hippocampal volume after severe traumatic brain injury in childhood. Pediatr Res 2005;58:302–308.
  59. Keenan HT, Runyan DK, Marshall SW, Nocera MA, Merten DF, Sinal SH: A population-based study of inflicted traumatic brain injury in young children. JAMA 2003;290:621– 626.
  60. Bruce DA, Zimmerman RA: Shaken impact syndrome: Pediatr Ann 1989;18:482–484, 486–489, 492–494.
  61. Duhaime AC, Christian C, Moss E, Seidl T: Long-term outcome in infants with the shaking-impact syndrome. Pediatr Neurosurg 1996;24:292–298.
  62. Duhaime AC, Christian CW, Rorke LB, Zimmerman RA: Nonaccidental head injury in infants – the ‘shaken-baby syndrome’. N Engl J Med 1998;338:1822–1829.
  63. Raghupathi R, Mehr MF, Helfaer MA, Margulies SS: Traumatic axonal injury is exacerbated following repetitive closed head injury in the neonatal pig. J Neurotrauma 2004;21:307–316.
  64. Parizel PM, Ceulemans B, Laridon A, Ozsarlak O, Van Goethem JW, Jorens PG: Cortical hypoxic-ischemic brain damage in shaken-baby (shaken impact) syndrome: value of diffusion-weighted MRI. Pediatr Radiol 2003;33:868–871.
  65. Gilliland MG: Interval duration between injury and severe symptoms in nonaccidental head trauma in infants and young children. J Forensic Sci 1998;43:723–725.
  66. King WJ, MacKay M, Sirnick A, Canadian Shaken Baby Study Group: Shaken baby syndrome in Canada: clinical characteristics and outcomes of hospital cases. CMAJ 2003;168:155–159.
  67. Duhaime AC, Gennarelli TA, Thibault LE, Bruce DA, Margulies SS, Wiser R: The shaken baby syndrome. A clinical, pathological, and biochemical study. J Neurosurg 1987;66:409–415.

    External Resources

  68. Shannon P, Smith CR, Deck J, Ang LC, Ho M, Becker L: Axonal injury and the neuropathology of shaken baby syndrome. Acta Neuropathol (Berl) 1998;95:625–631.
  69. Geddes JF, Vowles GH, Hackshaw AK, Nicklos CD, Scott IS, Whitwell HL: Neuropathology of inflicted head injury in children. 2. Microscopic brain injury in infants. Brain 2001;124:1299–1306.
  70. Ghatan S, Ellenbogen RG: Pediatric spine and spinal cord injury after inflicted trauma. Neurosurg Clin N Am 2002;13:227–233.
  71. Gleckman AM, Bell MD, Evans RJ, Smith TW: Diffuse axonal injury in infants with nonaccidental craniocerebral trauma: enhanced detection by beta-amyloid precursor protein immunohistochemical staining. Arch Pathol Lab Med 1999;123:146–151.
  72. Ruppel RA, Kochanek PM, Adelson PD, Rose ME, Wisniewski SR, Bell MJ, Clark RS, Marion DW, Graham SH: Excitatory amino acid concentrations in ventricular cerebrospinal fluid after severe traumatic brain injury in infants and children: the role of child abuse. J Pediatr 2001;138:1–3.
  73. Bell JM, Kochanek PM, Heyes MP, Wisniewski SR, Sinz EH, Clark RS, Blight AR, Marion DW, Adelson PD: Quinolinic acid in the cerebrospinal fluid of children after traumatic brain injury. Crit Care Med 1999;27:451–452.
  74. Berger RP, Heyes MP, Wisniewski SR, Adelson PD, Thomas N, Kochanek PM: Assessment of the macrophage marker quinolinic acid in cerebrospinal fluid after pediatric traumatic brain injury: insight into the timing and severity of injury in child abuse. J Neurotrauma 2004;21:1123–1130.
  75. Smith SL, Hall ED: Tirilazad widens the therapeutic window for riluzole-induced attenuation of progressive cortical degeneration in an infant rat model of shaken baby syndrome. J Neurotrauma 1998;15:707–719.
  76. Smith SL, Andrus PK, Gleason DD, Hall ED: Infant rat model of the shaken baby syndrome: preliminary characterization and evidence for the role of free radicals in cortical hemorrhaging and progressive neuronal degeneration. J Neurotrauma 1998;15:693–705.
  77. Bonnier C, Mesples B, Carpentier S, Henin D, Gressens P: Delayed white matter injury in a murine model of shaken baby syndrome. Brain Pathol 2002;12:320–328.
  78. Berger RP, Pierce MC, Wisniewski SR, Adelson PD, Kochanek PM: Serum S100B concentrations are increased after closed head injury in children: a preliminary study. J Neurotrauma 2002;19:1405–1409.
  79. Berger RP, Kochanek PM, Pierce MC: Biochemical markers of brain injury: could they be used as diagnostic adjuncts in cases of inflicted traumatic brain injury? Child Abuse Negl 2004;28:739–754.
  80. Berger RP, Adelson PD, Pierce MC, Dulani T, Cassidy LD, Kochanek PM: Serum neuron-specific enolase, S100B, and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children. J Neurosurg 2005;103:61–68.
  81. Berger RP, Dulani T, Adelson PD, Leventhal JM, Richichi R, Kochanek PM: Identification of brain injury in well-appearing infants using serum and cerebrospinal markers: a possible screening tool for inflicted traumatic brain injury. Pediatrics 2006;117:325–332.
  82. Jenny C, Hymel KP, Ritzen A, Reinert SE, Hay TC: Analysis of missed cases of abusive head trauma. JAMA 1999;281:621–626.
  83. Vavilala MS, Bowen A, Lam AM, Uffman JC, Powell J, Winn HR, Rivara FP: Blood pressure and outcome after severe pediatric traumatic brain injury. J Trauma 2003;55:1039–1044.
  84. White JR, Farukhi Z, Bull C, Christensen J, Gordon T, Paidas C, Nichols DG: Predictors of outcome in severely head-injured children. Crit Care Med 2001;29:534–540.
  85. Kroppenstedt SN, Kern M, Thomale UW, Schneider GH, Lanksch WR, Unterberg AW: Effect of cerebral perfusion pressure on contusion volume following impact injury. J Neurosurg 1999;90:520–526.
  86. Kochanek PM: Pediatric traumatic brain injury: beyond the guidelines; in Spinella G (ed): Current Treatment Options in Neurology. Philadelphia, Current Science, 2005, vol 7, pp 441–450.
  87. Downard C, Hulka F, Mullins RJ, Piatt J, Chesnut R, Quint P, Mann NC: Relationship of cerebral perfusion pressure and survival in pediatric brain-injured patients. J Trauma 2000;49:654–658; discussion 658–659.
  88. Robertson CS, Valadka AB, Hannay HJ, Contant CF, Gopiinath SP, Cormio M, Uzura M, Grossman RG: Prevention of secondary ischemic insults after severe head injury. Crit Care Med 1999;27:2086–2095.
  89. Chambers IR, Stobbart L, Jones PA, Kirkham FJ, Marsh M, Mendelow AD, Minns RA, Struthers S, Tasker RC: Age-related differences in intracranial pressure and cerebral perfusion pressure in the first 6 hours of monitoring after children’s head injury: association with outcome. Childs Nerv Syst 2005;21:195–199.
  90. Vavilala MS, Lee LA, Boddu K, Visco E, Newell DW, Zimmerman JJ, Lam AM: Cerebral autoregulation in pediatric traumatic brain injury. Pediatr Crit Care Med 2004;5:257–263.
  91. Wahlstrom MR, Olivecrona M, Koskinen LO, Rydenhag B, Naredi S: Severe traumatic brain injury in pediatric patients: treatment and outcome using an intracranial pressure targeted therapy – the Lund concept. Intensive Care Med 2005;31:832–839.
  92. Stahl N, Ungerstedt U, Nordstrom CH: Brain energy metabolism during controlled reduction of cerebral perfusion pressure in severe head injuries. Intensive Care Med 2001;27:1215–1223.
  93. Stiefel MF, Spiotta A, Gracias VH, Garuffe AM, Guillamondegui O, Maloney-Wilensky E, Bloom S, Grady MS, LeRoux PD: Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring. J Neurosurg 2005;103:805–811.
  94. Gupta AK, Hutchinson PJ, Al-Rawi P, Gupta S, Stewart M, Kirkpatrick PJ, Menon DK, Datta AK: Measuring brain tissue oxygenation compared with jugular venous oxygen saturation for monitoring cerebral oxygenation after traumatic brain injury. Anesth Analg 1999;88:549–553.
  95. Keenan HT, Nocera M, Bratton SL: Frequency of intracranial pressure monitoring in infants and young toddlers with traumatic brain injury. Pediatr Crit Care Med 2005;6:537–541.
  96. Hypothermia after Cardiac Arrest Study Group: Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549–556.
  97. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K: Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–563.
  98. Mansfield RT, Schiding JK, Hamilton RL, Kochanek PM: Effect of hypothermia on traumatic brain injury in immature rats. J Cereb Blood Flow Metab 1996;16:244–252.
  99. Clifton GL, Miller ER, Choi SC, Levin HS, McCauley S, Smith KR Jr, Muizelaar JP, Wagner FC Jr, Marion DW, Luerssen TG, Chestnut RM, Schwartz M: Lack of effect of hypothermia after acute brain injury. N Engl J Med 2001;344:556–563.
  100. Biswas AK, Bruce DA, Sklar FH, Bokovoy JL, Sommerauer JF: Treatment of acute traumatic brain injury in children with moderate hypothermia improves intracranial hypertension. Crit Care Med 2002;30:2742–2751.
  101. Adelson PD, Ragheb J, Kanev P, Brockmeyer D, Beers SR, Brown SD, Cassidy LD, Chang Y, Levin H: Phase II clinical trial of moderate hypothermia after severe traumatic brain injury in children. Neurosurgery 2005;56:740–754.
  102. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotton CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH; National Institute of Child Health and Human Development Neonatal Research Network: Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005;353:1574–1584.
  103. Figaji AA, Fieggen AG, Peter JC: Early decompressive craniotomy in children with severe traumatic brain injury. Childs Nerv Syst 2003;19:666–673.
  104. Hejazi N, Witzmann A, Fae P: Unilateral decompressive craniectomy for children with severe brain injury. Report of seven cases and review of the relevant literature. Eur J Pediatr 2002;161:99–104.
  105. Messing-Junger AM, Marzog J, Wobker G, Sabel M, Bock WJ: Decompressive craniotomy in severe brain injury. Zentralbl Neurochir 2003;64:171–177.
  106. Polin RS, Shaffrey ME, Bogaev CA, Tisdale N, Germanson T, Bocchicchio B, Jane JA: Decompressive bifrontal craniectomy in the treatment of severe refractory posttraumatic cerebral edema. Neurosurgery 1997;41:84–92.
  107. Cho DY, Wang YC, Chi CS: Decompressive craniotomy for acute shaken/impact baby syndrome. Pediatr Neurosurg 1995;23:192–198.
  108. Lea PM 4th, Faden AI: Traumatic brain injury: developmental differences in glutamate receptor response and the impact on treatment. Ment Retard Dev Disabil Rev 2001;7:235–248.
  109. Bittigau P, Sifringer M, Felderhoff-Muesser U, Hansen HH, Ikonomidou C: Neuropathological and biochemical features of traumatic injury in the developing brain. Neurotox Res 2003;5:475–490.
  110. Bayır H, Kagan VE, Tyurina YY, Tyurin VA, Ruppel RA, Adelson PD, Graham SH, Janesko K, Clark RSB, Kochanek PM: Assessment of antioxidant reserve and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatr Res 2002;51:571–578.
  111. Varma S, Janesko KL, Wisniewski SR, Bayır H, Adelson PD, Thomas NJ, Kochanek PM: F2-isoprostane and neuron-specific enolase in cerebrospinal fluid after severe traumatic brain injury in infants and children. J Neurotrauma 2003;20:781–786.
  112. Fan P, Yamauchi T, Noble LJ, Ferriero DM: Age-dependent differences in glutathione peroxidase activity after traumatic brain injury. J Neurotrauma 2003;20:437–445.
  113. Robertson CL: Mitochondrial dysfunction contributes to cell death following traumatic brain injury in adult immature animals. J Bioenerg Biomembr 2004;36:363–368.
  114. Scheff SW, Sullivan PG: Cyclosporin A significantly ameliorates cortical damage following experimental traumatic brain injury in rodents. J Neurotrauma 1999;16:783–792.
  115. Gilman CP, Mattson MP: Do apoptotic mechanisms regulate synaptic plasticity and growth-cone motility? Neuromolecular Med 2002;2:197–214.
  116. Prins ML, Fujima LS, Hovda DA: Age-dependent reduction of cortical contusion volume by ketones after traumatic brain injury. J Neurosci Res 2005;82:413–420.
  117. Armstead WM: Role of endothelin-1 in age-dependent cerebrovascular hypotensive responses after brain injury. Am J Physiol 1999;277:H1884–H1894.
  118. Griebach GS, Hovda DA, Molteni R, Gomez-Pinilla F: Alterations of BDNF and synapsin I within the occipital cortex and hippocampus after mild traumatic brain injury in the developing rat: reflections of injury-induced neuroplasticity. J Neurotrauma 2002;19:803–814.
  119. Porter RS: Alcohol and injury in adolescents. Pediatr Emerg Care 2000;16:316–320.
  120. Sachse KT, Jackson EK, Gillespie DG, Wisniewski S, Puccio A, Clark RSB, Dixon CE, Kochanek PM: Cerebrospinal fluid caffeine levels are increased and associated with favorable outcome after severe traumatic brain injury in humans. J Neurotrauma 2004;21:1326.

    External Resources

  121. Washington CB, Jackson EK, Gillespie D, Adelson PD, Wisniewski SR, Janesko KL, Clark RSB, Kochanek PM: Increased theobromine concentration in cerebrospinal fluid is associated with favorable outcome in infants and children after severe traumatic brain injury. Proceedings of the 2005 Pediatric Academic Societies’ Annual Meeting.
  122. Roof RL, Duvdeani R, Stein DG: Gender influences outcome of brain injury: progesterone plays a protective role. Brain Res 1993;607:333–336.
  123. Du L, Bayır H, Lai Y, Zhang Z, Kochanek PM, Watkins SC, Graham SH, Clark RSB: Innate gender-based proclivity in response to cytotoxicity and programmed cell death pathway. J Biol Chem 2004;279:38563–38570.
  124. Igarashi T, Huang TT, Noble LJ: Regional vulnerability after traumatic brain injury: gender differences in mice that overexpress human copper, zinc superoxide dismutase. Exp Neurol 2001;172:332–341.
  125. Bayır H, Marion DW, Puccio AM, Wisniewski SR, Janesko KL, Clark RSB, Kochanek PM: Marked gender effect on lipid peroxidation after severe traumatic brain injury in adult patients. J Neurotrauma 2004;21:1–8.
  126. Morrison WE, Arbelaez JJ, Fackler JC, De Maio A, Paidas CN: Gender and age effects on outcome after pediatric traumatic brain injury. Pediatr Crit Care Med 2004;5:145–151.
  127. Adelson PD, Bratton SL, Carney NA, Chesnut RM, du Coudray HE, Goldstein B, Kochanek PM, et al: Guidelines for the acute medical management of severe traumatic brain injury in infants, children and adolescents. Chapter 19. The role of anti-seizure prophylaxis following severe pediatric traumatic brain injury. 2003;4(suppl 3):S72–S75.

Pay-per-View Options
Direct payment This item at the regular price: USD 9.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 8.00