Scafidi Susanna, Jernberg Jennifer, Fiskum Gary, McKenna Mary C
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Department of Anesthesiology, Center for Shock Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Metabolites. 2022 Jul 29;12(8):710. doi: 10.3390/metabo12080710.
Traumatic brain injury (TBI) is leading cause of morbidity in young children. Acute dysregulation of oxidative glucose metabolism within the first hours after injury is a hallmark of TBI. The developing brain relies on ketones as well as glucose for energy. Thus, the aim of this study was to determine the metabolism of ketones early after TBI injury in the developing brain. Following the controlled cortical impact injury model of TBI, 21-22-day-old rats were infused with [2,4-C]β-hydroxybutyrate during the acute (4 h) period after injury. Using ex vivo C-NMR spectroscopy, we determined that C-β-hydroxybutyrate (C-BHB) metabolism was increased in both the ipsilateral and contralateral sides of the brain after TBI. Incorporation of the label was significantly higher in glutamate than glutamine, indicating that C-BHB metabolism was higher in neurons than astrocytes in both sham and injured brains. Our results show that (i) ketone metabolism was significantly higher in both the ipsilateral and contralateral sides of the injured brain after TBI; (ii) ketones were extensively metabolized by both astrocytes and neurons, albeit higher in neurons; (iii) the pyruvate recycling pathway determined by incorporation of the label from the metabolism of C-BHB into lactate was upregulated in the immature brain after TBI.
创伤性脑损伤（TBI）是幼儿发病的主要原因。损伤后最初几小时内氧化葡萄糖代谢的急性失调是TBI的一个标志。发育中的大脑依赖酮类和葡萄糖作为能量来源。因此，本研究的目的是确定发育中的大脑在TBI损伤后早期酮类的代谢情况。在TBI的控制性皮质撞击损伤模型之后，在损伤后的急性期（4小时）给21 - 22日龄的大鼠输注[2,4-C]β-羟基丁酸。使用离体碳核磁共振波谱，我们确定TBI后大脑的同侧和对侧C-β-羟基丁酸（C-BHB）代谢均增加。标记物在谷氨酸中的掺入显著高于谷氨酰胺，表明在假手术组和损伤组大脑中，神经元中的C-BHB代谢均高于星形胶质细胞。我们的结果表明：（i）TBI后损伤大脑的同侧和对侧酮类代谢均显著升高；（ii）星形胶质细胞和神经元均广泛代谢酮类，尽管在神经元中代谢更高；（iii）由C-BHB代谢的标记物掺入乳酸所确定的丙酮酸循环途径在TBI后的未成熟大脑中上调。
