Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
J Neurotrauma. 2011 Feb;28(2):245-57. doi: 10.1089/neu.2010.1639. Epub 2011 Jan 27.
Although diffuse brain damage has been suggested to be the predominant predictor of neurological morbidity following closed head injury in infants and children, the presence of contusions also predicts long-term neurobehavioral dysfunction. Contusive brain trauma in the 17-day-old rat resulted in neurodegeneration and caspase activation in the cortex at 1 day, and in the thalamus at 3 days post-injury, and to a greater extent following a deeper impact. Cortical tissue loss in the 4-mm impact group was significantly greater than that in the 3-mm impact group (p < 0.05), and exhibited a time-dependent increase over the first 3 weeks post-injury. Traumatic axonal injury was observed in the white matter tracts below the site of impact at 1 day, and in the corpus callosum at 3 days, to a greater extent following 4-mm impact. In contrast, cellular caspase-3 activation in these white matter tracts was only observed at 24 h post-injury and was not affected by impact depth. Similarly, neurodegeneration and caspase activation in the hippocampus was restricted to the dentate gyrus and occurred to a similar extent in both injured groups. Only the 4-mm impact group exhibited learning deficits in the first week (p < 0.0001) that was sustained until the third week post-injury (p < 0.0001), while deficits in the 3-mm impact group were seen only at 3 weeks post-injury (p < 0.02). These observations demonstrate that increasing severity of injury in immature animals does not uniformly increase the extent of cellular damage, and that the progression of tissue damage and behavioral deficits varies as a function of injury severity.
尽管弥漫性脑损伤被认为是婴儿和儿童闭合性颅脑损伤后神经发病率的主要预测因素，但挫伤的存在也预测长期神经行为功能障碍。17 日龄大鼠的挫伤性脑损伤导致 1 天时皮质的神经退行性变和半胱氨酸天冬氨酸蛋白酶激活，3 天时丘脑的神经退行性变和半胱氨酸天冬氨酸蛋白酶激活更严重，且损伤程度更深。4mm 撞击组的皮质组织损失明显大于 3mm 撞击组（p<0.05），并在损伤后前 3 周内呈时间依赖性增加。1 天时在撞击部位下方的白质束中观察到创伤性轴索损伤，3 天时在胼胝体中观察到创伤性轴索损伤，4mm 撞击组更严重。相比之下，这些白质束中细胞半胱氨酸天冬氨酸蛋白酶-3 的激活仅在损伤后 24 小时观察到，且不受撞击深度的影响。同样，海马中的神经退行性变和半胱氨酸天冬氨酸蛋白酶激活仅限于齿状回，且在两组损伤中程度相似。只有 4mm 撞击组在第一周（p<0.0001）出现学习缺陷，这种缺陷持续到损伤后第三周（p<0.0001），而 3mm 撞击组仅在第三周（p<0.02）出现学习缺陷。这些观察结果表明，在不成熟动物中，损伤严重程度的增加并不均匀地增加细胞损伤的程度，而且组织损伤和行为缺陷的进展随损伤严重程度而变化。
