Upregulated protein O-GlcNAcylation promoted functional and structural recovery of the contused spinal cord injury in rats by Thiamet-G treatment

Objectives-Elevated protein O-GlcNAcylation could benefit cell survival and promote organ functional recovery. Thiamet-G (O-GlcNAcase inhibitor) could upregulate protein O-GlcNAcylation level to improve dyskinesia in models of neurodegenerative diseases without any obvious detrimental side-effects. Therefore, we conducted this study to investigate the effects of protein O-GlcNAcylation upregulation by Thiamet-G on the spinal cord injury (SCI) in rats. Methods-We randomly assigned 74 rats to three groups: sham-operated group (Sham) with no lesion (n = 22), injured control group (SCI+SS) with saline solution (n = 26), and Thiamet-G treated group (SCI+Thiamet-G) (n = 26). We assessed Locomotor behavior using the Basso, Beattice, and Bresnahan (BBB) scale and evaluated histopathological alterations by morphometry and histochemistry. We also assessed potential inflammatory effects by microglia/macrophages immunohistochemistry, and potential apoptosis effects by caspase-3 western blot. Results-Thiamet-G treatment improved hindlimb motor functional recovery by inducing elevated protein O-GlcNAcylation, and mitigated the severity, reduced the lesion size and promoted the structural recovery of the injured spinal cord. Thiamet-G treatment also inhibited microglia/macrophages infiltration at the injury sites and the caspase-3 mediated apoptosis pathway. Discussion-We conclude that Thiamet-G induced elevated protein O-GlcNAcylation to ameliorate acute SCI, which could provide a potential novel therapeutic approach for SCI treatment.