Protective Effect Of Curcumin On Demyelination Of Nerve Fiber By Inhibiting Oligodendrocyte Apoptosis In Compreesed Spinal Cord Injury

Demyelination is initiated by oligodendrocyte apoptosis through endoplasmic reticulum-mitochondria interactions and enhanced by the expression of DNA-binding inhibitor 2 (Id2) following compressed spinal cord injury (CSCI). Curcumin, which belongs to the curcuminoid family, is a yellow phenolic pigment abstracted from the powdered rhizome of Curcuma longa. A recent study has proven that curcumin exhibits neuroprotective effects against traumatic spinal cord injury by inhibiting neuronal apoptosis. However, the ability of curcumin to protect CSCI from demyelination by inhibiting oligodendrocyte apoptosis has not been reported.Objective:To explore the effect of curcumin on demyelination induced by CSCI and explore its mechanism.Methods:Adult healthy Sprague-Dawley (SD) 64 rats were randomly divided into the sham (n=24), vehicle (n=20), and treatment (n =20) groups.The rats in sham group were not subjected to any experimental procedure. The rats in the treatment and vehicle groups were subjected to laminectomy without compression. Neurological function assessment, osmic acid staining and TEM were performed to observe the motor function of rats and pathological changes of myelinated in white matter. The expressions of caspase-3 and CNPase were observe by double labeling immunofluorescence. The expressions of MBP, activated caspase-3, caspase-12 and cytochrome c were detected by western blot.Results:BBB scores in the vehicle group were lower than those in the sham and treatment groups (vehicle group vs. sham group, p<0.05; vehicle group vs. treatment group, p<0.05). Osmic acid staining and transmission electron microscopy showed that the swelling degree of myelin sheaths in the treatment group was milder than that in the vehicle group. The layers of myelin sheaths in the treated group were also more compact than those in the vehicle group. LFB staining results showed that the myelinated nerve fibers in the posterior and anterior funiculus were disordered, and the number of remaining myelinated nerve fibers decreased in the vehicle group. However, the above pathological phenomena were significantly addressed in the treatment group compared with the vehicle group (vehicle group vs. sham group, p<0.05; vehicle group vs. treatment group, p<0.05). Double-labeling immunofluorescence showed activated caspase-3-positive oligodendrocytes in the vehicle group. By contrast, these oligodendrocytes were significantly decreased in the treatment group. Western blot results also showed that the expression of activated caspase-3, caspase-12, and cytochrome c in the vehicle group was significantly higher than that in the sham and treatment groups (p<0.05). The MBP expression in the vehicle group was significantly lower than that in the sham and treatment groups (p <0.05), which was consistent with the number of the remaining myelin sheaths.Conclusion:The protective potential of curcumin against CSCI is partly attributed to its anti-apoptotic effects on oligodendrocytes.