Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury

@article{Lee2009SustainedDO,
  title={Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury},
  author={Hyunjung Lee and Robert J. Mckeon and Ravi V. Bellamkonda},
  journal={Proceedings of the National Academy of Sciences},
  year={2009},
  volume={107},
  pages={3340 - 3345}
}
Chondroitin sulfate proteoglycans (CSPGs) are a major class of axon growth inhibitors that are up-regulated after spinal cord injury (SCI) and contribute to regenerative failure. Chondroitinase ABC (chABC) digests glycosaminoglycan chains on CSPGs and can thereby overcome CSPG-mediated inhibition. But chABC loses its enzymatic activity rapidly at 37 °C, necessitating the use of repeated injections or local infusions for a period of days to weeks. These infusion systems are invasive, infection… Expand
Self-assembling peptide hydrogels for the stabilization and sustained release of active Chondroitinase ABC in vitro and in spinal cord injuries.
TLDR
Two self-assembling peptides (SAPs), featuring different self-assembled nanostructures, and on different methods of drug loading to exploit the neuroregenerative potential of Chondroitinase ABC, a thermolabile pro-plastic agent attenuating the inhibitory action of CSPGs showed great promise for the delivery of Ch ABC in future therapies targeting chronic SCI. Expand
Local Delivery of High-Dose Chondroitinase ABC in the Sub-Acute Stage Promotes Axonal Outgrowth and Functional Recovery after Complete Spinal Cord Transection
TLDR
This study demonstrates that high-dose ChABC treatment in the sub-acute stage of SCI effectively improves glial scar digestion by reducing the lesion size and increasing axonal regrowth to the related functional nuclei, which promotes locomotor recovery. Expand
Controlled release of chondroitinase ABC from fibrin gel reduces the level of inhibitory glycosaminoglycan chains in lesioned spinal cord.
TLDR
When highly concentrated fibrin gel containing Ch ABC was implanted adjacent to a spinal cord lesion, bioactive ChABC was detectable in the spinal cord for at least three weeks, and 3 weeks after injury the level of inhibitory GAG found in injured spinal cord treated with the delivery system was 37% lower than thelevel of GAG in spinal Cord treated with an injection of ChABC. Expand
Sustained dual drug delivery of anti-inhibitory molecules for treatment of spinal cord injury.
Myelin-associated inhibitors (MAIs) and chondroitin sulfate proteoglycans (CSPGs) are major contributors to axon growth inhibition following spinal cord injury and limit functional recovery. TheExpand
Sustained Delivery of Chondroitinase ABC from Hydrogel System
TLDR
An agarose-carbomer hydrogel was investigated as a delivery system capable of an effective chABC administration and confirmed to be a feasible tool for chABC delivery and a promising device for spinal cord injury topic repair strategies. Expand
Affinity-based release of chondroitinase ABC from a modified methylcellulose hydrogel.
TLDR
An affinity-based system that sustained the release of bioactive ChABC for at least 7days and has the potential to be used as a platform technology for the release and detection of other proteins that can be expressed using a similar construct is designed. Expand
Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair.
TLDR
The results clearly demonstrated the feasibility of incorporating NT-3 and ChABC via mTG immobilization to produce protein-incorporated collagen nanofibers for SCI treatment. Expand
Thermosensitive collagen/fibrinogen gels loaded with decorin suppress lesion site cavitation and promote functional recovery after spinal cord injury
TLDR
The development of a novel, flowable, thermosensitive, injectable drug delivery system that forms a solid BC/FB gel that can be used to deliver reparative drugs, such as the naturally occurring anti-inflammatory, anti-scarring agent Decorin, into adult rat spinal cord lesion sites is reported. Expand
Peripheral Nerve Grafts and Chondroitinase ABC Application Improves Functional Recovery After Complete Spinal Cord Transection
TLDR
This study showed that PNGs can establish a good anatomical bridge after SCI and set the stage for functional recovery, and the combination of PNGs and ChABC restored significantly better locomotor function than controls. Expand
Local delivery of chondroitinase ABC with or without stromal cell-derived factor 1α promotes functional repair in the injured rat spinal cord.
TLDR
A crosslinked methylcellulose hydrogel for minimally invasive, localized, and sustained intrathecal drug delivery resulted in faster and more sustained behavioural improvement over time than other groups, and significantly reduced chondroitin sulfate proteoglycan levels and greater distribution of NPCs throughout the spinal cord tissue with ChABC delivery may explain the improved locomotor function. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 46 REFERENCES
Chondroitinase ABC promotes axonal re-growth and behavior recovery in spinal cord injury.
TLDR
In the animal trials, ChABC-treatment could improve motor function through BBB locomotor's test and reduce limiting ability of scar tissues to promote axonal regeneration via changing the structure of CSPGs by immunohistochemistry with GAP-43. Expand
Chondroitinase ABC Digestion of the Perineuronal Net Promotes Functional Collateral Sprouting in the Cuneate Nucleus after Cervical Spinal Cord Injury
TLDR
Results demonstrate, for the first time, a functional change directly linked to anatomical evidence of sprouting by spinal cord afferents after chABC treatment, in the chABC-treated rats. Expand
Chondroitinase ABC promotes functional recovery after spinal cord injury
TLDR
It is demonstrated that CSPGs are important inhibitory molecules in vivo and suggested that their manipulation will be useful for treatment of human spinal injuries. Expand
Chondroitinase ABC Promotes Sprouting of Intact and Injured Spinal Systems after Spinal Cord Injury
TLDR
Robust sprouting is found of both injured and intact descending projections as well as uninjured primary afferents after a cervical dorsal column injury and ChABC treatment and CSPG degradation; compensatory sprouting of descending systems could be a key mechanism underlying functional recovery. Expand
Single, high-dose intraspinal injection of chondroitinase reduces glycosaminoglycans in injured spinal cord and promotes corticospinal axonal regrowth after hemisection but not contusion.
TLDR
It is proposed that improved axonal growth in hemisected spinal cords is due to decreased inhibition resulting from degradation of CSPGs located adjacent to severed CST axons, suggesting that other inhibitors of axonalgrowth persist in the gliotic regions. Expand
Functional Axonal Regeneration through Astrocytic Scar Genetically Modified to Digest Chondroitin Sulfate Proteoglycans
TLDR
A local efficacy for reduced CSPG to enhance CNS axon growth after traumatic injury is confirmed, implying that combination-based therapy will be especially advantageous for CNS injuries. Expand
Chondroitinase ABCI improves locomotion and bladder function following contusion injury of the rat spinal cord.
TLDR
It is demonstrated that chondroitinase is effective at promoting both somatic and autonomic motor recovery following a clinically relevant contusion spinal Cord injury and is a candidate as a therapeutic for human spinal cord injury. Expand
In situ gelling hydrogels for conformal repair of spinal cord defects, and local delivery of BDNF after spinal cord injury.
TLDR
It is suggested that these thermo-reversible scaffolds have great potential to serve as growth permissive 3D scaffolds, and to present neurotrophic factors and potentially anti-scar agents to the injury site and enhance regeneration after spinal cord injury. Expand
Chondroitinase ABC enhances axonal regrowth through Schwann cell‐seeded guidance channels after spinal cord injury
  • C. Chau, D. Shum, +5 authors Xm Xu
  • Chemistry, Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2004
TLDR
It is concluded that CS glycoforms deposited during gliosis at the distal graft–host interface could be cleared by the in vivo action of chondroitinase ABC to improve prospects of axonal regeneration into the host spinal cord. Expand
Combining an Autologous Peripheral Nervous System “Bridge” and Matrix Modification by Chondroitinase Allows Robust, Functional Regeneration beyond a Hemisection Lesion of the Adult Rat Spinal Cord
TLDR
Results demonstrate, for the first time, that modulation of extracellular matrix components after spinal cord injury promotes significant axonal regeneration beyond the distal end of a PN bridge back into the spinal cord and that regenerating axons can mediate the return of useful function of the affected limb. Expand
...
1
2
3
4
5
...