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

## TL;DR

A ketogenic diet before spinal cord injury in rats improves recovery by protecting mitochondria through a specific pathway.

## Contribution

The study reveals that KD pretreatment enhances SCI recovery via the PGC-1α/Sirt1/Nrf1 pathway and mitochondrial protection.

## Key findings

- KD pretreatment improved neuromotor recovery and reduced neuronal apoptosis in SCI rats.
- PGC-1α, Sirt1, and Nrf1 expression was upregulated in the KD group compared to the standard diet group.
- KD alleviated mitochondrial dysfunction by regulating TOMM20 expression in spinal cord tissues.

## Abstract

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.

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.

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.

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.