EphB2 knockdown decreases the formation of astroglial-fibrotic scars to promote nerve regeneration after spinal cord injury in rats

Aims At the beginning of spinal cord injury (SCI), the expression of EphB2 on fibroblasts and ephrin-B2 on astrocytes increased simultaneously and their binding triggers the formation of astroglial-fibrotic scars, which represent a barrier to axonal regeneration. In the present study, we sought to suppress scar formation and to promote recovery from SCI by targeting EphB2 in vivo. Methods The female rats SCI models were used in vivo experiments by subsequently injecting with EphB2 shRNA lentiviruses. The effect on EphB2 knockdown was evaluated at 14 days after injury. The repair outcomes were evaluated at 3 months by electrophysiological and morphological assessments to regenerated nerve tissue. The EphB2 expression and TGF-beta 1 secretion were detected in vitro using a lipopolysaccharides (LPS)-induced astrocyte injury model. Results RNAi decreased the expression of EphB2 after SCI, which effectively inhibited fibroblasts and astrocytes from aggregating at 14 days. The expression of EphB2 in activated astrocytes, in addition to fibroblasts, was significantly increased after SCI in vivo, in line with upregulated expression of EphB2 and increased secretion of TGF-beta 1 in astrocyte culture treated with LPS. Compared to the scramble control, RNAi targeting with EphB2 could promote more nerve regeneration and better myelination. Conclusions EphB2 knockdown may effectively inhibit the formation of astroglial-fibrotic scars at the beginning of SCI. It is beneficial to eliminate the barrier of nerve regeneration.

Automated summary

Targeting EphB2 can effectively inhibit the formation of astroglial-fibrotic scars at the beginning of SCI, promoting nerve regeneration.