Specific necroptosis inhibitor-1(Nec-1) attenuates glial scar formation in rat models with spinal cord injury

Abstract

Objective To observe the effect of necroptosis inhibitor-1(Nec-1) on glial scar formation in rats with spinal cord injury and its mechanism. Methods The rats were randomly divided into sham group, model group (falling method) and RIPK1 inhibitor Nec-1 group (10 μmol/L Nec-1 10μL was injected into lateral ventricle). BBB method was used to measure the motor function of hind limbs, immunofluorescence was used to detect the formation of glial scar, and Western blot was used to detect the expression of cathepsin B, caspase-3, GFAP and vimentin. Results On the 14th day after operation, compared with the sham group, the BBB scores of the model group and Nec-1 group were significantly lower (P＜0.05), compared with the model group, the BBB score of Nec-1 group was significantly higher (P＜0.05). NF-200 fluorescence was not found in the sham operation group, but in the model group and Nec-1 group, the intensity of NF-200 fluorescence labeling in Nec-1 group decreased significantly(P＜0.05). On the 7th and 14th day after operation, compared with the sham operation group, the protein level of cathepsin B, caspase-3, GFAP and vimentin in the model group and Nec-1 group was significantly higher(P＜0.05),while the protein level of cathepsin B, caspase-3, GFAP and vimentin in Nec-1 group decreased significantly (P＜0.05). Conclusions Nec-1 may regulate expression level of cathepsin B and caspase-3, reduce the expression of GFAP and vimentin proteins, reduce the formation of glial scar after spinal cord injury and promote the recovery of neural function.

Keywords

• spinal cord injury|glial scar|necroptosis inhibitor-1(nec-1)|cathepsin b