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Metabolic reprogramming: a new option for the
treatment of spinal cord injury
Jiangjie Chen, Jinyang Chen, Chao Yu, Kaishun Xia, Biao Yang, Ronghao Wang, Yi Li, Kesi Shi, Yuang Zhang, Haibin Xu, Xuesong Zhang, Jingkai Wang, Qixin Chen, Chengzhen Liang
2025, 20 (4):
1042-1057.
doi: 10.4103/NRR.NRR-D-23-01604
Spinal cord injuries impose a notably economic burden on society, mainly because of the
severe after-effects they cause. Despite the ongoing development of various therapies
for spinal cord injuries, their effectiveness remains unsatisfactory. However, a deeper
understanding of metabolism has opened up a new therapeutic opportunity in the form
of metabolic reprogramming. In this review, we explore the metabolic changes that occur
during spinal cord injuries, their consequences, and the therapeutic tools available for
metabolic reprogramming. Normal spinal cord metabolism is characterized by independent
cellular metabolism and intercellular metabolic coupling. However, spinal cord injury results
in metabolic disorders that include disturbances in glucose metabolism, lipid metabolism,
and mitochondrial dysfunction. These metabolic disturbances lead to corresponding
pathological changes, including the failure of axonal regeneration, the accumulation of
scarring, and the activation of microglia. To rescue spinal cord injury at the metabolic level,
potential metabolic reprogramming approaches have emerged, including replenishing
metabolic substrates, reconstituting metabolic couplings, and targeting mitochondrial
therapies to alter cell fate. The available evidence suggests that metabolic reprogramming
holds great promise as a next-generation approach for the treatment of spinal cord injury.
To further advance the metabolic treatment of the spinal cord injury, future efforts should
focus on a deeper understanding of neurometabolism, the development of more advanced
metabolomics technologies, and the design of highly effective metabolic interventions.
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