Weeks Dianne, Sullivan Sarah, Kilbaugh Todd, Smith Colin, Margulies Susan S
1 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.
J Neurotrauma. 2014 Jan 15;31(2):206-14. doi: 10.1089/neu.2013.3113. Epub 2013 Dec 5.
This study investigated the age-dependent injury response of diffuse traumatic axonal injury (TAI) and regional subdural and subarachnoid intracranial hemorrhage (ICH) in two pediatric age groups using a porcine head injury model. Fifty-five 5-day-old and 40 four-week-old piglets-which developmentally correspond to infants and toddlers, respectively-underwent either a sham injury or a single rapid non-impact rotational injury in the sagittal plane and were grouped by post-TBI survival time (sham, 3-8 h, one day, 3-4 days, and 5-6 days). Both age groups exhibited similar initial levels of ICH and a significant reduction of ICH over time (p<0.0001). However, ICH took longer to resolve in the five-day-old age group. At 5-6 days post-injury, ICH in the cerebrum had returned to sham levels in the four-week-old piglets, while the five-day-olds still had significantly elevated cerebral ICH (p=0.012). Both ages also exhibited similar resolution of axonal injury with a peak in TAI at one day post-injury (p<0.03) and significantly elevated levels even at 5-6 days after the injury (p<0.008), which suggests a window of vulnerability to a second insult at one day post-injury that may extend for a prolonged period of time. However, five-day-old piglets had significantly more TAI than four-week-olds overall (p=0.016), which presents some evidence for an increased vulnerability to brain injury in this age group. These results provide insight into an optimal window for clinical intervention, the period of increased susceptibility to a second injury, and an age dependency in brain injury tolerance within the pediatric population.
本研究使用猪头部损伤模型,调查了两个儿科年龄组中弥漫性创伤性轴索损伤(TAI)以及局部硬膜下和蛛网膜下颅内出血(ICH)的年龄依赖性损伤反应。55只5日龄和40只4周龄的仔猪(分别在发育上对应于婴儿和幼儿)接受了假损伤或矢状面单次快速非撞击性旋转损伤,并根据创伤性脑损伤(TBI)后的存活时间分组(假损伤组、3 - 8小时组、1天组、3 - 4天组和5 - 6天组)。两个年龄组的ICH初始水平相似,且ICH随时间显著减少(p<0.0001)。然而,5日龄年龄组的ICH消退时间更长。在受伤后5 - 6天,4周龄仔猪大脑中的ICH已恢复到假损伤水平,而5日龄仔猪的大脑ICH仍显著升高(p = 0.012)。两个年龄组的轴索损伤消退情况也相似,TAI在受伤后1天达到峰值(p<0.03),即使在受伤后5 - 6天水平仍显著升高(p<0.008),这表明受伤后1天存在对二次损伤的易损窗口,且可能会持续较长时间。然而,总体而言,5日龄仔猪的TAI比4周龄仔猪显著更多(p = 0.016),这为该年龄组对脑损伤易感性增加提供了一些证据。这些结果为临床干预的最佳窗口、对二次损伤易感性增加的时期以及儿科人群脑损伤耐受性的年龄依赖性提供了见解。