Therapeutic Effect Of Deacetylase SIRT1 And Its Predictive Value For Long-term Neurological Recovery In Spinal Cord Injury

Posttraumatic Inflammation is the major component of secondary injury and is thought to be a verified available target to improve neuron survive and locomotor function.SIRT1 have been shown to play an critical role in regulating inflammation.Here,using pharmacological interventions(SRT1720)and genetic knockout,we investigated the therapeutics role and mechanisms of SIRT1 in spinal cord injury(SCI).We evaluated whether serum levels of SIRT1 protein act as a biomarker for traumatic spinal cord injury(SCI).First,we found that administration of SRT1720,an agonist of SIRT1,to WT mice significantly improved functional recovery for up to 28 d post-injury by reducing the levels of pro-inflammatory cytokines,the number of M1 macrophages,the number of macrophages/microglia,and the accumulation of perivascular macrophages.In contrast,administration of SRT1720 to SIRT1 knockout(KO)mice did not improve locomotor recovery or attenuate inflammation.SIRT1 KO mice exhibited worse locomotor recovery than those of WT mice after SCI.Our results showed that serum SIRT1 levels increased from 5 d to 21 d in Mild,Moderate and Severe SCI groups(n=9/group).There was a significant correlation of mouse serum SIRT1 7 d or 10 d post-injury and distant neurological recovery 28 d after SCI(7 d: r=0.63,p<0.001;10 d: r=0.74,p<0.001).Serum SIRT1 levels at 7 and 9 d correlated with the motor outcome 12 months after SCI(7 d: r=-0.81,p<0.001;9 d:r=-0.74,p<0.001).Therefore,we conclude that SIRT1 plays a key role in the regulation of neurological inflammation after SCI injury,which may be a new therapeutic target for SCI.Serum SIRT1 may be a useful experimental tool to stratify injury severity and predict neurological recovery in SCI patients.