Bisperoxovanadium protects against spinal cord injury by regulating autophagy via activation of ERK1/2 signaling

Abstract

Background

Spinal cord injury (SCI) is a disease of the central nervous system with few restorative treatments. Autophagy has been regarded as a promising therapeutic target for SCI. The inhibitor of phosphatase and tensin homolog deleted on chromosome ten (PTEN) bisperoxovanadium (bpV[pic]) had been claimed to provide a neuroprotective effect on SCI; but the underlying mechanism is still not fully understood.

Materials and methods

Acute SCI model were generated with SD Rats and were treated with control, acellular spinal cord scaffolds (ASC) obtained from normal rats, bpV(pic), and combined material of ASC and bpV(pic). We used BBB score to assess the motor function of the rats and the motor neurons were stained with Nissl staining. The expressions of the main autophagy markers LC3B, Beclin1 and P62, expressions of apoptosis makers Bax, Bcl2, PARP and Caspase 3 were detected with IF or Western Blot analysis.

Results

The bpV(pic) showed significant improvement in functional recovery by activating autophagy and accompanied by decreased neuronal apoptosis; combined ASC with bpV(pic) enhanced these effects. In addition, after treatment with ERK1/2 inhibitor SCH772984, we revealed that bpV(pic) promotes autophagy and inhibits apoptosis through activating ERK1/2 signaling after SCI.

Conclusion

These results illustrated that the bpV(pic) protects against SCI by regulating autophagy via activation of ERK1/2 signaling.

Keywords:

• bisperoxovanadium
• spinal cord injury
• autophagy
• apoptosis
• ERK1/2 signaling

Acknowledgments

This work was supported by the National Natural Science Foundation of China (approval number: 81560213) and supported by 2018GXNSFAA138074.

Disclosure

The authors report no conflicts of interest in this work.