Mechanisms of Secondary Damage after Severe Traumatic Brain Injury in Infants and Children: The Role of Child Abuse
Patrick M. Kochanek, P.I.

Through a grant from the Center for Disease Control-funded University of Pittsburgh Center for Injury Control and Research, we have established a cerebrospinal fluid (CSF) bank from infants and children with severe traumatic brain injury. We have used this valuable resource, coupled to demographic, physiologic, and outcome data, to begin to unravel the complex pathobiology of this disease process. The diagram below outlines the studies that have been carried out thus far in this important area of work. The database that we have collected has been instrumental not only for characterizing individual biochemical, cellular or molecular mechanisms of damage but also for studying the interactions between these mediator systems. We are collaborating with a large number of laboratories both at the University of Pittsburgh and worldwide to quantify a broad array of mediators of secondary damage and repair. An additional finding of this work has been that we are defining a unique biochemical, cellular and molecular response in infants who are victims of the shaken baby syndrome.

Figure 1. Mediators quantified by our group in CSF from infants and children with severe traumatic brain injury. A vertical arrow to the right of the mediator indicates it is increased after injury. A yellow arrow connecting to shaken baby syndrome indicates an association with this form of injury. Note, endogenous neuroprotectants are low in abuse victims.

Figure 2. Pediatric Critical Care fellow Dr. Randall Ruppel prepares a cerebrospinal fluid sample for testing.

Selected publications resulting from this work include:

1. Bell M, Kochanek PM, Doughty LA, et al: Interleukin-6 and Interleukin-10 in Cerebrospinal Fluid after Traumatic Brain Injury in Children. J Neurotrauma 14:451-457, 1997.

2. Whalen MJ, Carlos TM, Kochanek PM, et al: Soluble Adhesion Molecules in CSF After Severe Head Injury in Children. J Neurotrauma 15:777-787, 1998.

3. Bell MJ, Kochanek PM, Heyes M, et al: Quinolinic Acid in Cerebrospinal Fluid of Children After Traumatic Brain Injury. Crit Care Med 27:493-497, 1999.
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4. Whalen MJ, Carlos TM, Kochanek PM, et al: Interleukin-8 is Increased in CSF of Children with Severe Head Injury. Crit Care Med (in press).

5. Clark RSB, Kochanek PM, Adelson PD, et al: Increases in Bcl-2 protein in cerebrospinal fluid and evidence for programmed-cell death in infants and children following severe traumatic brain injury. J Pediatrics (in press).

6. Ruppel RA, Kochanek PM, Adelson PD, et al: Excitotoxicity after severe traumatic brain injury in infants and children: The Role of Child Abuse. J Pediatrics (in revision).

7. Bell M, Adelson PD, Doughty LA, et al: Comparison of the Interleukin-6 and Interleukin-10 Response in Children After Severe Traumatic Brain Injury or Septic Shock. Acta Neurochir Suppl 70:96-97, 1997.

8. Ruppel R, Kochanek P, Adelson PD, et al: Excitotoxicity After Severe Traumatic Brain Injury (TBI) in Infants and Children: The Role of Child Abuse. (101.11). Press Release - Society for Neuroscience 28th Annual Meeting, November 7 - 12, 1998.

9. Kochanek PM, Clark RSB, Ruppel RA, et al: 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 (in press).

10. Robertson CL, Bell MJ, Kochanek PM, et al: Increased adenosine in cerebrospinal fluid after traumatic brain injury in infants and children. J Neurotrauma 16:975, 1999.

11. DeKosky ST, Ikonomovic MD, Wisniewski S, et al: Post-trauma levels of cytokines and growth factors in adult and pediatric CSF. J Neurotrauma 16:994, 1999.

12. Ruppel RA, Kochanek PM, Adelson PD, et al: Endothelin-1 is increased in cerebrospinal fluid following traumatic brain injury in children. Crit Care Med 27:A76, 1999.

13. Robertson C, Bell M, Kochanek P, et al: Increased adenosine concentration in cerebrospinal fluid after severe traumatic brain injury in infants and children: association with severity of injury. Crit Care Med 27:A38, 1999.

14. Robertson C, Minamino N, Ruppel R, et al: Increased adrenomedullin in cerebrospinal fluid after traumatic brain injury in children: a preliminary report. Crit Care Med 27:A75, 1999.

15. Seidberg NA, Clark RSB, Kochanek PM, et al: Soluble Fas is increased in CSF from infants and children after head injury. Crit Care Med 27:A38, 1999.

16. Han YH, Carcillo JA, Ruppel RA, et al: Cerebrospinal fluid procalcitonin is increased after traumatic brain injury in children. Crit Care Med 27:A75, 1999.

    For a synopsis of our work in this area, please see our recent invited review published as the first article in the inaugural issue of the journal Pediatric Critical Care Medicine.
    
    Kochanek PM, Clark RSB, Ruppel RA, et al: 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 (in press).

Collaborators (alphabetical order):

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