This review aims to discuss examples of changes in glucose (sugar) metabolism after traumatic brain injury (TBI). It will attempt to provide an understanding of what changes in glucose metabolism mean for the injured brain. It will further identify potential therapeutic target(s) emanating from our growing understanding of glucose pathways and their roles in TBI.
Although a significant fraction of glucose is utilized for the energy production in the brain, a small fraction is utilized in other, often ignored pathways. Recent studies have unraveled unexpected biological effects of glucose through these pathways, including redox regulation, genetic and epigenetic regulation, glycation of proteins, nucleotide synthesis and amino acid synthesis.
A number of regulatory players in minor glucose metabolic pathways, such as folate and chondroitin sulfate proteoglycans, have recently been identified as potential targets to restore cognitive functions. Targeting of these players should be combined with the supplementation of alternative energy substrates to achieve the maximal cognitive restoration after TBI. This multimodal therapeutic strategy deserves testing in various models of TBI.
Supplemental digital video content 1: Video that demonstrates an effective therapeutic strategy for the cognitive restoration after TBI.