Developmental neuroscience
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Impact-induced head injury in infants results in acute focal contusions and traumatic axonal injury (TAI) that are associated with chronic holohemispheric cortical and white matter atrophy and may contribute to poor outcome in brain-injured children less than 4 years of age. Contusive brain trauma in postnatal day (PND) 11 or PND 17 rat pups, ages neurologically equivalent to a human infant and toddler, respectively, leads to cortical tissue loss and white matter atrophy which are associated with cognitive deficits. In adult models of brain trauma and in brain-injured humans, acute and sustained activation of the calpain family of calcium-activated neutral proteases has been implicated in neuronal death and TAI. ⋯ Axonal accumulation of amyloid precursor protein, indicative of TAI, was observed in the corpus callosum and lateral aspects of the white matter below the site of impact, and in the thalamus in PND 11 rats only. Intra-axonal calpain activation was observed to a limited extent in the corpus callosum and subcortical white matter tracts in both brain-injured PND 11 and PND 17 rats. Collectively, these results provide evidence that calpain activation may participate in neuronal loss in the injured cortex, but may not contribute to the pathogenesis of TAI following contusive brain trauma in the immature rat.
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Randomized Controlled Trial Multicenter Study
Hypothermia pediatric head injury trial: the value of a pretrial clinical evaluation phase.
The utility of a pretrial clinical evaluation or run-in phase prior to conducting trials of complex interventions such as hypothermia therapy following severe traumatic brain injury in children and adolescents has not been established. ⋯ The pretrial clinical evaluation phase was useful to ensure compliance with complex hypothermia therapy and consensus-based clinical management guidelines of care successfully implemented across 17 of 18 centers. This study maneuver allowed us to complete a subsequent RCT in 225 children following severe traumatic brain injury.
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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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Traumatic brain injury (TBI) is the leading cause of death and disability in children. Evidence-based guidelines for the management of this population are available; however, the data highlight significant deficiencies with few treatment standards or guidelines. Considering the limited availability of resources, it is necessary to define realistic goals. Attention should be given to injury prevention, developing standardized pediatric admission and outcome evaluations, increasing the utility and spectrum of physiological and biochemical testing, and defining the evolving role of imaging in TBI.
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The objective of this study was to utilize tissue deformation thresholds associated with acute axonal injury in the immature brain to predict the duration of unconsciousness. Ten anesthetized 3- to 5-day-old piglets were subjected to nonimpact axial rotations (110-260 rad/s) producing graded injury, with periods of unconsciousness from 0 to 80 min. Coronal sections of the perfusion-fixed brain were immunostained with neurofilament antibody (NF-68) and examined microscopically to identify regions of swollen axons and terminal retraction balls. ⋯ The thresholds for 80 and 90% probability of predicting injury were found to correlate better with injury severity than those for 50%, and the product of strain and strain rate was the best predictor of injury severity (p=0.02). Predictive capacity of the linear relationship was confirmed with additional (n=13) animal experiments. We conclude that the suprathreshold injured volume can provide a satisfactory prediction of injury severity in the immature brain.