The role of Sonic Hedgehog pathway in the development of spinal cord injury in rat model

Abstract The purpose of this study was to explore whether and how the Shh pathway exert a neuroprotective effect in SCI. The SCI model of rat was established by a Allen's weight-drop method. Thirty rats were divided into 5 groups as follows: Control, Sham, SCI model, SCI + Shh activator, and SCI + Shh inbibitor. Rats in group of Shh activator or inbibitor were administrated with purmorphamine (10 mg/kg) or cyclopamine (10 mg/kg) respectively daily within one week after establishment of SCI model. Scores of BBB and Reuter were evaluated at the time-points of 1st, 3rd, 5th and 7th day. The pathological injury, the levels of IL-1β and TNF-α and the protein and mRNA expressions of Gli1, Shh and Smoothened in spinal cord tissue were assessed on 7th day, respectively. Rat treated with purmorphamine exhibited a significant increase in BBB score in comparison with SCI group. Interestingly, purmorphamine treatment declined SCI-induced increases in the levels of IL-1 β and TNF-α, whereas cyclopamine administration up-regulated their expressions of these inflammatory cytokines. The pyknotic neuronal cells in gray matter area of the spinal cord and the area of cavity in white matter area were reduced in purmorphamine treatment when compared with SCI group, whereas treatment with cyclopamine elicited an opposite changes. In conclusion, this study demonstrated that Shh activator plays an important protective role in the development of SCI in rat model, which might provide a new strategy via targeting Shh pathway to prevent or treat SCI in the future.