Glial scarring limits recovery following decompressive surgery in rats with syringomyelia

Abstract

Syringomyelia is a neurological disease that is difficult to cure, and treatments often have limited effectiveness. In this study, a rat model of syringomyelia induced by epidural compression was used to investigate the factors that limit the prognosis of syringomyelia. After we treated syringomyelia rats with surgical decompression alone, MRI revealed that the syringomyelia rats did not show the expected therapeutic effect. Through cerebrospinal fluid (CSF) tracing experiments, we found that the CSF flow in the subarachnoid space (SAS) of rats was restored after decompression. This shows that the poor prognosis of syringomyelia rats in this study is not caused by CSF circulation disorders, suggesting the existence of other factors. Further, immunofluorescence revealed that there were extensive glial scars characterized by increased expression of glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs) around the syrinx in the non-improved group compared to the improved group. To verify the limiting role of glial scarring in the prognosis of syringomyelia, we intervened with the selective astrocyte inhibitor fluorocitrate (FC). Intrathecal injection of FC significantly inhibited the formation of glial scar after decompression in syringomyelia rats and promoted the reduction of syrinx. This scar-inhibiting effect significantly improved neuronal survival, promoted axonal and myelin recovery, and showed better recovery in sensory function and fine motor control functions. These findings suggest that glial scarring around syrinx is a key factor limiting recovery of syringomyelia. By inhibiting glial scar formation, the prognosis of syringomyelia can be significantly improved, which provides a new strategy for improving clinical treatment effects.

Keywords: Decompression surgery; Fluorocitrate; Glial scar; Subarachnoid space; Syringomyelia; Syrinx.