Open AccessFeasible stabilization of chondroitinase abc enables reduced astrogliosis in a chronic model of spinal cord injury
Author(s) -
Raspa Andrea,
Bolla Edoardo,
Cuscona Claudia,
Gelain Fabrizio
Publication year - 2019
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12984
Subject(s) - astrogliosis , spinal cord injury , in vivo , chemistry , regeneration (biology) , glycosaminoglycan , chondroitin sulfate , sucrose , gliosis , cytotoxicity , lesion , spinal cord , pharmacology , in vitro , biochemistry , central nervous system , medicine , microbiology and biotechnology , neuroscience , surgery , biology , pathology
Summary Aims Usually, spinal cord injury ( SCI ) develops into a glial scar containing extracellular matrix molecules including chondroitin sulfate proteoglycans ( CSPG s). Chondroitinase ABC (Ch ABC ), from Proteus vulgaris degrading the glycosaminoglycan ( GAG ) side chains of CSPG s, offers the opportunity to improve the final outcome of SCI . However, Ch ABC usage is limited by its thermal instability, requiring protein structure modifications, consecutive injections at the lesion site, or implantation of infusion pumps. Methods Aiming at more feasible strategy to preserve Ch ABC catalytic activity, we assessed various stabilizing agents in different solutions and demonstrated, via a spectrophotometric protocol, that the 2.5 mol/L Sucrose solution best stabilized Ch ABC as far as 14 days in vitro. Results Ch ABC activity was improved in both stabilizing and diluted solutions at +37°C, that is, mimicking their usage in vivo. We also verified the safety of the proposed aqueous sucrose solution in terms of viability/cytotoxicity of mouse neural stem cells ( NSC s) in both proliferating and differentiating conditions in vitro. Furthermore, we showed that a single intraspinal treatment with Ch ABC and sucrose reduced reactive gliosis at the injury site in chronic contusive SCI in rats and slightly enhanced their locomotor recovery. Conclusion Usage of aqueous sucrose solutions may be a feasible strategy, in combination with rehabilitation, to ameliorate Ch ABC ‐based treatments to promote the regeneration of central nervous system injuries.