Extracellular matrix remodelling in degenerative cervical myelopathy

Degenerative cervical myelopathy (DCM), a type of spinal cord injury triggered by chronic compression from degenerative changes of the spine, induces pathophysiological changes similar to traumatic spinal cord injury, including reactive gliosis, demyelination and neuron loss. However, the effects of chronic spinal cord compression on extracellular matrix composition and organization remain uncharacterized. Here, we analyse untreated post-mortem human tissue and a mouse model of chronic spinal cord compression using immunohistochemical and transcriptomic approaches to assess chondroitin sulphate proteoglycan (CSPG) and fibrosis-related matrix deposition. In human post-mortem tissue, astrogliosis, CSPG accumulation and fibrotic collagen deposition were elevated in the DCM cases (n = 7) compared to controls (n = 5), though gliosis and fibrosis-related matrix deposition were not significantly associated with the degree of cord compression. The mouse model, however, demonstrated more distinct border-forming astrocyte phenotypes. Transcriptional and histological markers of vascular and interstitial fibrosis were also significantly increased in the mouse model. These findings demonstrate that astroglial CSPG deposition and fibrotic scarring occur in DCM, albeit potentially in a more diffuse pattern than in traumatic spinal cord injury. Moreover, this study supports previous observations of vascular fibrotic thickening in DCM.