Apoptotic neurodegeneration in the context of traumatic injury to the developing brain

Abstract

Head trauma is the leading cause of death and disability in the pediatric population. Some recent studies on neuropathological and biochemical features of traumatic injury to the developing brain revealed interesting aspects and potential targets for future research. Trauma triggers both excitotoxic and apoptotic neurodegeneration in the developing rat brain. Apoptotic neurodegeneration occurs in a delayed fashion over several days and contributes in an age-dependent fashion to neuropathologic outcome following head trauma, with the immature brain being exceedingly sensitive. Biochemical studies indicate that both the extrinsic and the intrinsic apoptotic pathways are involved in pathogenesis of apoptotic cell death following trauma in the developing brain and that caspase inhibition ameliorates apoptotic neurodegeneration in an infant head trauma model. Given the major contribution of apoptotic neurodegeneration to neuropathologic outcome following trauma to the developing brain, interference with apoptotic pathways may comprise a potential therapeutic target in pediatric traumatic brain injury.