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Neuropathological and biochemical features of traumatic injury in the developing brain

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Abstract

Trauma to the developing brain constitutes a poorly explored field. Some recent studies attempting to model and study pediatric head trauma, the leading cause of death and disability in the pediatric population, revealed interesting aspects and potential targets for future research.

Trauma triggers both excitotoxic and apoptotic neurodegeneration in the developing rat brain. Excitotoxic neurodegeneration develops and subsides rapidly (within hours) whereas apoptotic cell death occurs in a delayed fashion over several days following the initial traumatic insult. Apoptotic neurodegeneration contributes in an age-dependent fashion to neuronal injury following head trauma, with the immature brain being exceedingly sensitive. In the most vulnerable ages the apoptosis contribution to the extent of traumatic brain damage far outweighs that of the excitotoxic component.

Molecular and biochemical studies indicate that both extrinsic and intrinsic mechanisms are involved in pathogenesis of apoptotic cell death following trauma. Interestingly, in infant rats a pancaspase inhibitor ameliorated apoptotic neurodegeneration with a therapeutic time window of up to 8 h after trauma.

These results help explain unfavorable outcomes of very young pediatric head trauma patients and imply that regimen which target slow active forms of cell death may comprise a successful neuroprotective approach.

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  1. Department of Pediatric Neurology, Charité Children's Hospital, Humboldt University, Augustenburger Platz 1, 13353, Berlin, Germany

    Petra Bittigau, Marco Sifringer, Henrik H. Hansen & Chrysanthy Ikonomidou

  2. Department of Neonatology, Charité Children's Hospital, Humboldt University, Augustenburger Platz 1, 13353, Berlin, Germany

    Ursula Felderhoff-Mueser

  3. Department of Pharmacology, The Danish University of Pharmaceutical Sciences, DK-2100, Copenhagen, Denmark

    Henrik H. Hansen

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  1. Petra Bittigau
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Correspondence to Chrysanthy Ikonomidou.

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Bittigau, P., Sifringer, M., Felderhoff-Mueser, U. et al. Neuropathological and biochemical features of traumatic injury in the developing brain. neurotox res 5, 475–490 (2003). https://doi.org/10.1007/BF03033158

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