Artikel
Soft alginate hydrogel alters scar formation and promotes locomotor recovery after spinal cord injury in a rat hemimyelonectomy model
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Veröffentlicht: | 21. Mai 2013 |
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Objective: The treatment of traumatic spinal cord injury (SCI) and the consecutive devastating neurological sequelae have an enormous individual and economic impact. Among other approaches, implantation of functionalized hydrogels is very promising, because they can serve as a matrix for the regenerating tissue, carry and release bioactive molecules and various cell types. Recently, we demonstrated that soft alginate hydrogel supported neurite outgrowth and protected neurons against oxidative stress in vitro. The purpose of the current study was to investigate the effects of such soft alginate hydrogels on locomotor recovery in a hemimyelonectomy model of spinal cord injury in rats
Method: A rat SCI model consisted of a left-sided hemimyelonectomy (2 or 4 mm gaps) at the thoracic vertebral level 9. Four groups were built: 1) rats with 2 mm gaps and soft alginate (n=8), 2) vehicle control with 2 mm gap (n=11), 3) rats with 4 mm gaps and soft alginate (n=8), and 4) vehicle control with 4 mm gap (n=7). The animals were assessed in a variety of behavioral tests consisting of open field (BBB score), swimming (Louisville Swim score, LSS), and narrow beam walking (cm). Immunohistochemical staining with GFAP, Iba1, GAP43, Cy3, β-II-Tubulin as well as anterograde axonal labeling were performed to assess the degree of axonal regeneration and posttraumatic scar formation.
Results: 2 mm-alginate-rats demonstrated significantly improved locomotor recovery compared to vehicle controls detectable already 10 days after SCI in LSS (p<0,01), and in BBB scores 70 (p<0.05) days, respectively. Also in the 4 mm-alginate-group, the animals performed better, albeit without statistical significance. Histological examination of spinal cords revealed that fibrous scarring was absent in spinal cord wounds of alginate-rats, but it was extensive in vehicle controls. Anterograde in vivo tracing of axons in chronic inflammatory phase revealed similar distribution of DiI-axons in vehicle controls and alginate-rats: DiI-labelling was abrogated at the wound margin, but was continuous on the lesion-free side of spinal cord.
Conclusions: Implantation of soft alginate hydrogel improved locomotor recovery in rats after SCI and inhibited fibrous and glial scarring of spinal cord wound region.