Acute Putrescine Supplementation with Schwann Cell Implantation Improves Sensory and Serotonergic Axon Growth and Functional Recovery in Spinal Cord Injured Rats.

J Bryan Iorgulescu,Andre R Sanchez,Christian M Andrade,Damien D Pearse,Samik P Patel,Jack Louro

doi:10.1155/2015/186385

J Bryan Iorgulescu, Andre R Sanchez + Show 4 more

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https://doi.org/10.1155/2015/186385

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Abstract

Schwann cell (SC) transplantation exhibits significant potential for spinal cord injury (SCI) repair and its use as a therapeutic modality has now progressed to clinical trials for subacute and chronic human SCI. Although SC implants provide a receptive environment for axonal regrowth and support functional recovery in a number of experimental SCI models, axonal regeneration is largely limited to local systems and the behavioral improvements are modest without additional combinatory approaches. In the current study we investigated whether the concurrent delivery of the polyamine putrescine, started either 30 min or 1 week after SCI, could enhance the efficacy of SCs when implanted subacutely (1 week after injury) into the contused rat spinal cord. Polyamines are ubiquitous organic cations that play an important role in the regulation of the cell cycle, cell division, cytoskeletal organization, and cell differentiation. We show that the combination of putrescine with SCs provides a significant increase in implant size, an enhancement in axonal (sensory and serotonergic) sparing and/or growth, and improved open field locomotion after SCI, as compared to SC implantation alone. These findings demonstrate that polyamine supplementation can augment the effectiveness of SCs when used as a therapeutic approach for subacute SCI repair.

Highlights

To date no treatment can completely reverse the clinical outcomes associated with spinal cord injury (SCI)
Based upon our previous studies demonstrating the ability of cyclic AMP elevation to improve the effectiveness of Schwann cell (SC) implants after SCI and the growing evidence that polyamine synthesis may mediate several of cyclic AMP’s downstream effects on axon regeneration [3, 4, 6], we investigated whether the supplementation of SC implants with putrescine, given either within 30 minutes or following a 1week delay after contusive SCI, could improve SC implanthost integration, axon growth support, and locomotor recovery in an experimental contusive SCI paradigm
Compared to the implant size in the SC only group (1.23 ± 0.07 mm2), those animals receiving putrescine administration beginning at the time of implantation exhibited 1.8-fold increase in implant area (2.24 ± 0.34 mm2; t33 = 3.391, p < 0.01; Figures 3(a), 3(c), and 3(d)) as identified using p75 immunochemistry [13]

Summary

Introduction

To date no treatment can completely reverse the clinical outcomes associated with spinal cord injury (SCI). Host cellular efforts to restrict progressive tissue injury, including glial reactivity, extracellular matrix deposition, and scar formation around the lesion site, subsequently give rise to a nonpermissive environment for axon regeneration and the endogenous recovery of function [1]. This extrinsic antagonism of neurorepair is compounded by a reduction in the intrinsic growth capacity of adult central neurons [2]. Finding novel therapeutics that combat secondary injury, overcome the growth-inhibiting environment of the lesion site, and/or enhance the intrinsic capacity of neurons to regenerate is imperative for restoring function after SCI. Strategies combining cellular with pharmacological, Neural Plasticity molecular, or biomaterial approaches have shown the most promise in overcoming these obstacles to attain meaningful anatomical and functional repair [3]

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