Pretreatment with a ketogenic diet inhibits mitochondrial damage in rat models of spinal cord injury via the PGC-1α/Sirt1/Nrf1 pathway.

OBJECTIVES: Spinal cord injury (SCI) often results in poor recovery prospects and a high disability rate. Although the ketogenic diet (KD) was suggested as a neuroprotective agent after SCI, its underlying mechanism remains unclear. MATERIALS AND METHODS: Rats were divided into three groups: sham-operated controls, SCI with standard diet (SD), and SCI with KD. Following a 2-week dietary pretreatment, the SD and KD groups underwent a cervical level 5 hemi-contusion injury, and their neuromotor functions were monitored for 28 days. The expression levels of PGC-1α, Sirt1, Nrf1, and TOMM20 in the spinal cord tissues were measured using qPCR and immunofluorescence staining. RESULTS: Compared with the SD group, KD pretreatment significantly improved neuromotor recovery and reduced neuronal apoptosis. The expression levels of PGC-1, Sirt1, and Nrf1 in the spinal cord tissues of rats in the KD group were significantly up-regulated. Additionally, KD was found to alleviate neuronal mitochondrial dysfunction by regulating TOMM20 expression. CONCLUSION: KD pretreatment enhances SCI recovery by modulating the PGC-1α/Sirt1/Nrf1 pathway, improving mitochondrial function, and reducing neuronal death. The study provides new insights into the mechanisms of KD.