Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
Department of Neurology, Children's National Health System, George Washington University, School of Medicine & Health Sciences, Washington, DC 20010, United States.
Exp Neurol. 2019 Jun;316:74-84. doi: 10.1016/j.expneurol.2019.03.018. Epub 2019 Apr 3.
Improved patient survival following pediatric traumatic brain injury (TBI) has uncovered a currently limited understanding of both the adaptive and maladaptive metabolic perturbations that occur during the acute and long-term phases of recovery. While much is known about the redundancy of metabolic pathways that provide adequate energy and substrates for normal brain growth and development, the field is only beginning to characterize perturbations in these metabolic pathways after pediatric TBI. To date, the majority of studies have focused on dysregulated oxidative glucose metabolism after injury; however, the immature brain is well-equipped to use alternative substrates to fuel energy production, growth, and development. A comprehensive understanding of metabolic changes associated with pediatric TBI cannot be limited to investigations of glucose metabolism alone. All energy substrates used by the brain should be considered in developing nutritional and pharmacological interventions for pediatric head trauma. This review summarizes post-injury changes in brain metabolism of glucose, lipids, ketone bodies, and amino acids with discussion of the therapeutic potential of altering substrate utilization to improve pediatric TBI outcomes.
儿童创伤性脑损伤 (TBI) 后患者生存率的提高，揭示了人们目前对急性和长期恢复期内适应性和失调性代谢紊乱的认识有限。尽管人们对为正常大脑生长和发育提供充足能量和底物的代谢途径的冗余性有了很多了解，但该领域才刚刚开始描述儿童 TBI 后的这些代谢途径的紊乱。迄今为止，大多数研究都集中在损伤后氧化葡萄糖代谢的失调上；然而，未成熟的大脑有能力使用替代底物来为能量产生、生长和发育提供燃料。对与儿童 TBI 相关的代谢变化的全面理解不能仅限于对葡萄糖代谢的研究。在制定针对儿童头部创伤的营养和药理学干预措施时，应考虑大脑使用的所有能量底物。本综述总结了脑损伤后葡萄糖、脂质、酮体和氨基酸的脑代谢变化，并讨论了改变底物利用以改善儿童 TBI 预后的治疗潜力。
