| Summary: | 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-<sup>13</sup>C]β-hydroxybutyrate during the acute (4 h) period after injury. Using ex vivo <sup>13</sup>C-NMR spectroscopy, we determined that <sup>13</sup>C-β-hydroxybutyrate (<sup>13</sup>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 <sup>13</sup>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 <sup>13</sup>C-BHB into lactate was upregulated in the immature brain after TBI.
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