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

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.