Peripheral Nerve Grafts and Chondroitinase ABC Application Improves Functional Recovery After Complete Spinal Cord Transection

Amgad Hanna, Katie E. Kaeppler, Mark E. Ehlers, Mahrokh Dadsetan, Michael J. Yaszemski, Ross D. Toigo, Junhwa Kim, Euhaa Hwang, Ernesto Bogarin-Miranda, Morgan M. Buchholz, Alexandra R. Springer, Daniel J. Hellenbrand

Abstract


Background: Peripheral nerve grafts (PNGs) in the spinal cord support axonal regeneration and functional recovery. Chondroitinase ABC (ChABC) has been used to break down chondroitin sulfate proteoglycans (CSPGs) that inhibit axonal regeneration. If ChABC is effectively delivered to the injury site, CSPGs can be broken down so axons can pass through the distal interface between the graft and the spinal cord before CSPG accumulation has an adverse impact on recovery. 

Methods: In this study, we tested the synergistic effect of using predegenerated PNGs as scaffolds for axonal growth, while delivering ChABC via oligo-(polyethylene glycol) fumarate (OPF) tubes, to promote functional recovery after complete spinal cord injury in rats. 

Results: Our results show that: 1) PNGs anatomically incorporated into the spinal cord after a complete transection, 2) thousands of axons regenerated into the PNGs, 3) cholera toxin-B labeled axons crossed through the graft, and 4) the combination of PNGs and ChABC restored significantly better locomotor function than controls. 

Conclusions: Our study showed that PNGs can establish a good anatomical bridge after SCI and set the stage for functional recovery. 




doi: http://dx.doi.org/10.4021/jnr209w


Keywords


Chondroitinase ABC; Glial scar; Wallerian Degeneration; Oligo-(polyethylene glycol) fumarate

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