Traumatic Injury to the Immature Brain: Inflammation, Oxidative Injury, and Iron-Mediated Damage as Potential Therapeutic Targets

Mathew B. Potts, Seong E. Koh, William D. Whetstone, Breset A. Walker, Tomoko Yoneyama, Catherine P. Claus, Hovhannes M. Manvelyan, Linda J. Noble-Haeusslein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)143-153
Number of pages11
JournalNeuroRx
Volume3
Issue number2
DOIs
StatePublished - Apr 2006

Keywords

  • Traumatic brain injury
  • immature brain
  • inflammation
  • iron
  • oxidative damage

ASJC Scopus subject areas

  • Pharmacology (medical)

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