In this review, five questions serve as the framework to discuss the importance of age-related differences in the pathophysiology and therapy of traumatic brain injury (TBI). The following questions are included: (1) Is diffuse cerebral swelling an important feature of pediatric TBI and what is its etiology? (2) Is the developing brain more vulnerable than the adult brain to apoptotic neuronal death after TBI and, if so, what are the clinical implications? (3) If the developing brain has enhanced plasticity versus the adult brain, why are outcomes so poor in infants and young children with severe TBI? (4) What contributes to the poor outcomes in the special case of inflicted childhood neurotrauma and how do we limit it? (5) Should both therapeutic targets and treatments of pediatric TBI be unique? Strong support is presented for the existence of unique biochemical, molecular, cellular and physiological facets of TBI in infants and children versus adults. Unique therapeutic targets and enhanced therapeutic opportunities, both in the acute phase after injury and in rehabilitation and regeneration, are suggested.
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