The Ketone Metabolite β-Hydroxybutyrate Attenuates Oxidative Stress in Spinal Cord Injury by Suppression of Class I Histone Deacetylases.

The ketone metabolite β-hydroxybutyrate (βOHB), is reported to be neuroprotective after spinal cord injury (SCI) in rats, but the underlying mechanism remains unknown. The present study aims to investigate effects of βOHB on suppression of oxidative stress and inhibition of class I histone deacetylases (HDACs) in in vivo and in vitro models. Rats were fed with ketogenic diet (KD) or standard diet (SD) for 3 weeks. A C5 hemi-contusion injury was applied to these animals on the 14th day of experiment, and spinal cord samples were harvested on the 1st, 3rd and 7th days after SCI, respectively. The blood ketone levels were significantly higher in the KD groups. KD reduced oxidative stress markers and reactive oxygen species (ROS) products, downregulated the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)2 and NOX4, and upregulated the expression of forkhead box group O (FOXO)3a, mitochondrial superoxide dismutase (MnSOD), and catalase after SCI. The in vitro study, performed on PC12 cells, indicated that βOHB inhibited H