Distinct Glycosylation Responses to Spinal Cord Injury in Regenerative and Nonregenerative Models

Abstract

Traumatic spinal cord injury (SCI) results in disruption of tissue integrity and loss of function. We hypothesize that glycosylation has a role in determining the occurrence of regeneration and that biomaterial treatment can influence this glycosylation response. We investigated the glycosylation response to spinal cord transection in Xenopus laevis and rat. Transected rats received an aligned collagen hydrogel. The response compared regenerative success, regenerative failure, and treatment in an established nonregenerative mammalian system. In a healthy rat spinal cord, ultraperformance liquid chromatography (UPLC) N-glycoprofiling identified complex, hybrid, and oligomannose N-glycans. Following rat SCI, complex and outer-arm fucosylated glycans decreased while oligomannose and hybrid structures increased. Sialic acid was associated with microglia/macrophages following SCI. Treatment with aligned collagen hydrogel had a minimal effect on the glycosylation response. In Xenopus , lectin histochemistry revealed increased levels of N -acetyl-glucosamine (GlcNAc) in premetamorphic animals. The addition of GlcNAc is required for processing complex-type glycans and is a necessary foundation for additional branching. A large increase in sialic acid was observed in nonregenerative animals. This work suggests that glycosylation may influence regenerative success. In particular, loss of complex glycans in rat spinal cord may contribute to regeneration failure. Targeting the glycosylation response may be a promising strategy for future therapies.

MS-based glycomics: An analytical tool to assess nervous system diseases

“…Recent studies have related glial scars to neurodegenerative disease including AD ( D’Ambrosi and Apolloni, 2020 ). Glycosylation changes have been observed and linked to spinal cord regeneration with a decrease of complex glycans in spinal cord injury models ( Ronan et al, 2022 ). In addition, the sulfation pattern of glycosaminoglycans was also observed to be altered in active gliosis in animal models after brain injuries ( Alonge et al, 2021 ).…”