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NeuroRX

, Volume 3, Issue 2, pp 143–153 | Cite as

Traumatic injury to the immature brain: Inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets

  • Mathew B. Potts
  • Seong-Eun Koh
  • William D. Whetstone
  • Breset A. Walker
  • Tomoko Yoneyama
  • Catherine P. Claus
  • Hovhannes M. Manvelyan
  • Linda J. Noble-HaeussleinEmail author
Article

Summary

Traumatic brain injury (TBI) is the leading cause of morbidity and mortality among children and both clinical and experimental data reveal that the immature brain is unique in its response and vulnerability to TBI compared to the adult brain. Current therapies for pediatric TBI focus on physiologic derangements and are based primarily on adult data. However, it is now evident that secondary biochemical perturbations play an important role in the pathobiology of pediatric TBI and may provide specific therapeutic targets for the treatment of the head-injured child. In this review, we discuss three specific components of the secondary pathogenesis of pediatric TBI — inflammation, oxidative injury, and iron-induced damage — and potential therapeutic strategies associated with each. The inflammatory response in the immature brain is more robust than in the adult and characterized by greater disruption of the blood-brain barrier and elaboration of cytokines. The immature brain also has a muted response to oxidative stress compared to the adult due to inadequate expression of certain antioxidant molecules. In addition, the developing brain is less able to detoxify free iron after TBI-induced hemorrhage and cell death. These processes thus provide potential therapeutic targets that may be tailored to pediatric TBI, including anti-inflammatory agents such as minocycline, antioxidants such as glutathione peroxidase, and the iron chelator deferoxamine.

Key Words

Traumatic brain injury immature brain inflammation oxidative damage iron 

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2006

Authors and Affiliations

  • Mathew B. Potts
    • 1
  • Seong-Eun Koh
    • 1
  • William D. Whetstone
    • 2
  • Breset A. Walker
    • 2
  • Tomoko Yoneyama
    • 1
  • Catherine P. Claus
    • 1
  • Hovhannes M. Manvelyan
    • 1
  • Linda J. Noble-Haeusslein
    • 1
    Email author
  1. 1.Department of Neurological SurgeryUniversity of CaliforniaSan Francisco
  2. 2.Department of Medicine (Division of Emergency Medicine)University of CaliforniaSan Francisco

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