Developmental neuroscience
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Mitochondria play a central role in cerebral energy metabolism, intracellular calcium homeostasis and reactive oxygen species generation and detoxification. Following traumatic brain injury (TBI), the degree of mitochondrial injury or dysfunction can be an important determinant of cell survival or death. Literature would suggest that brain mitochondria from the developing brain are very different from those from mature animals. ⋯ This review will focus on four main areas of secondary injury after pediatric TBI, including excitotoxicity, oxidative stress, alterations in energy metabolism and cell death pathways. Specifically, we will describe what is known about developmental differences in mitochondrial function in these areas, in both the normal, physiologic state and the pathologic state after pediatric TBI. The ability to identify and target aspects of mitochondrial dysfunction could lead to novel neuroprotective therapies for infants and children after severe TBI.
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The objective of this study was to describe the incidence of impaired cerebral autoregulation and to describe the relationship between impaired cerebral autoregulation and outcome after severe pediatric traumatic brain injury (TBI). We prospectively examined cerebral autoregulation in 28 children
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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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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.
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Based on recent work demonstrating age-dependent ketogenic neuroprotection after traumatic brain injury (TBI), it was hypothesized that the neuroprotection among early post-weaned animals was related to induced cerebral transport of ketones after injury. Regional changes in monocarboxylate transporter 2 (MCT2) were acutely examined with immunohistochemistry after sham surgery or controlled cortical impact injury among postnatal day 35 and adult rats. ⋯ Using Western blotting, MCT2 expression was 80-88% greater in microvessels isolated from postnatal day 35 rats at all time points relative to adults. The increased MCT2 expression was temporally correlated with an age-related increase in cerebral uptake of ketones, when ketones were made available after injury.