Pretreatment with a ketogenic diet inhibits mitochondrial damage in rat models of spinal cord injury via the PGC-۱α/Sirt۱/Nrf۱ pathway

Objective(s): 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 ۲-week dietary pretreatment, the SD and KD groups underwent a cervical level ۵ hemi-contusion injury, and their neuromotor functions were monitored for ۲۸ days. The expression levels of PGC-۱α, Sirt۱, Nrf۱, and TOMM۲۰ 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-۱, Sirt۱, and Nrf۱ 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 TOMM۲۰ expression.Conclusion: KD pretreatment enhances SCI recovery by modulating the PGC-۱α/Sirt۱/Nrf۱ pathway, improving mitochondrial function, and reducing neuronal death. The study provides new insights into the mechanisms of KD.

کلیدواژه ها:

Apoptosis ، Ketogenic diet ، Mitochondria ، Sirtuin ۱ ، Spinal cord injury