1 Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior , Mattel Children's Hospital at UCLA, and the UCLA Steve Tisch BrainSPORT Program, Los Angeles, California.
2 NeuroSpectroScopics, LLC , Sherman Oaks, California.
J Neurotrauma. 2018 Jul 15;35(14):1637-1645. doi: 10.1089/neu.2017.5366. Epub 2018 May 18.
Diffuse axonal injury contributes to the long-term functional morbidity observed after pediatric moderate/severe traumatic brain injury (msTBI). Whole-brain proton magnetic resonance echo-planar spectroscopic imaging was used to measure the neurometabolite levels in the brain to delineate the course of disruption/repair during the first year post-msTBI. The association between metabolite biomarkers and functional measures (cognitive functioning and corpus callosum [CC] function assessed by interhemispheric transfer time [IHTT] using an event related potential paradigm) was also explored. Pediatric patients with msTBI underwent assessments at two times (post-acutely at a mean of three months post-injury, n = 31, and chronically at a mean of 16 months post-injury, n = 24). Healthy controls also underwent two evaluations, approximately 12 months apart. Post-acutely, in patients with msTBI, there were elevations in choline (Cho; marker for inflammation and/or altered membrane metabolism) in all four brain lobes and the CC and decreases in N-acetylaspartate (NAA; marker for neuronal and axonal integrity) in the CC compared with controls, all of which normalized by the chronic time point. Subgroups of TBI showed variable patterns chronically. Patients with slow IHTT had lower lobar Cho chronically than those with normal IHTT; they also did not show normalization in CC NAA whereas those with normal IHTT showed significantly higher levels of CC NAA relative to controls. In the normal IHTT group only, chronic CC Cho and NAA together explained 70% of the variance in long-term cognitive functioning. MR based whole brain metabolic evaluations show different patterns of neurochemistry after msTBI in two subgroups with different outcomes. There is a dynamic relationship between prolonged inflammatory responses to brain damage, reparative processes/remyelination, and subsequent neurobehavioral outcomes. Multimodal studies allow us to test hypotheses about degenerative and reparative processes in patient groups that have divergent functional outcome, with the ultimate goal of developing targeted therapeutic agents.
弥漫性轴索损伤导致儿童中度/重度创伤性脑损伤（msTBI）后长期功能障碍。全脑质子磁共振回波平面波谱成像用于测量脑内神经代谢物水平，以描绘 msTBI 后第一年期间的破坏/修复过程。还探讨了代谢物生物标志物与功能测量（认知功能和胼胝体[CC]功能，通过事件相关电位范式用半球间转移时间[IHTT]评估）之间的关系。接受 msTBI 的儿科患者在两个时间点进行评估（受伤后平均三个月的急性期，n=31，受伤后平均 16 个月的慢性期，n=24）。健康对照组也接受了两次评估，大约相隔 12 个月。急性期，msTBI 患者所有四个脑叶和 CC 的胆碱（Cho；炎症和/或改变的膜代谢标志物）升高，与对照组相比，CC 的 N-乙酰天冬氨酸（NAA；神经元和轴突完整性标志物）降低，所有这些标志物在慢性时间点都恢复正常。慢性组中 TBI 亚组表现出不同的模式。IHTT 较慢的患者慢性期脑叶 Cho 水平低于 IHTT 正常的患者；他们的 CC NAA 也没有恢复正常，而 IHTT 正常的患者的 CC NAA 水平明显高于对照组。只有在 IHTT 正常的组中，慢性 CC Cho 和 NAA 共同解释了长期认知功能的 70%的变化。基于磁共振的全脑代谢评估显示，两个结局不同的亚组的 msTBI 后神经化学具有不同的模式。脑损伤后持续的炎症反应、修复过程/髓鞘形成以及随后的神经行为结果之间存在动态关系。多模态研究使我们能够在具有不同功能结局的患者组中测试关于退行性和修复性过程的假设，最终目标是开发靶向治疗药物。
