Brain injury is common with high mortality and morbidity, with implications for both society and individuals in terms of cost, loss of production and long‐term impairment [1]. The cellular and molecular events initiated by cerebral injury are complex, restricting the precision of characterization into primary, secondary and long term as the durations of pathogenic events are variable and can overlap. Following injury, cellular energetics play a vital role in maintaining cerebral homeostasis [2]. A better understanding of the impact of substrate supply on the injured brain may help improve management following brain injury and provide novel therapeutic options.

The adult brain consumes approximately 20% of basal metabolism, most of which is provided by the oxidation of 100–120 g of glucose/24 h [3]. However, in times of starvation or injury, the primary cerebral metabolic substrates may alter. Following traumatic brain injury (TBI), a number of biochemical changes take place in the brain, which diverts the processing of glucose via the normal pathways.

The purpose of this chapter is to examine cerebral energetics and alternative substrates capable of supplying cerebral energy requirements (Table 1).