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Copolymer Surfactant Poloxamer 188 Accelerates Post-axonotemetic Sciatic Nerve Regeneration

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Abstract

Purpose

Trauma-mediated peripheral nerve axon injury invariably involves structural alteration of the axonal plasmalemma cell membrane. Increased axonal membrane permeability to electrolytes results in metabolic stress and axonal degeneration if the axon does not seal. Poloxamer 188 (P188) is a linear multiblock copolymer composed of a hydrophobic polyoxypropylene (POP) block in the middle with polyethylene glycol (PEG) blocks on both ends. The central POP block concentrates at sites of cell membrane disruption and catalyzes sealing of disrupted cellular membranes. We tested the hypothesis that intravenously administered P188 (9800 Da, 0.2 mM) can accelerate distal axon recovery after sciatic nerve crush injury using an established axonotemetic model.

Methods

A crush injury was performed on the sciatic nerve of thirty female Sprague-Dawley rats. Rats were randomized to receive either 0.2 mM P188 or Dextran, administered 1 h after crush injury. Compound nerve action potentials (CNAP) and density of neurofilament distal to the point of injury were analyzed on post-crush day (PCD) 4, 14, and 21.

Results

A significant improvement in axonal conduction for animals treated with P188 was observed for PCD 4 and PCD 14 (p < 0.01). The segment of axon distal to the site of injury in the P188-treated group demonstrated significant increase in nerve fiber density on PCD4 (p < 0.01).

Conclusion

Therefore, a single dose of intravenous P188 administered 1 h after crush injury to rat sciatic nerve resulted in more rapid structural and functional nerve recovery.

Lay Summary

Nerve injuries are common in day-to-day physical trauma. On a molecular level, nerve injury is precipitated by damage to the nerve’s cell membrane, which disrupts the delicate balance of the cellular environment and leads to cell death. There are molecules that can repair ruptured cell membranes by inserting themselves into it and effectively resealing the cell. Copolymer P188 is one such molecules which can be injected intravenously and selectively targets injured cell membranes. In this study, we tested the hypothesis that copolymer P188 injected intravenously into rats following peripheral nerve injury could facilitate the functional recovery of the nerve.

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Data Availability

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Acknowledgments

The authors would like to acknowledge Zhen-Du Zhang, PhD, and Neil D. Dalal, MD, for their contributions to this project and the A.J. Carlson Animal Research Facilities at the University of Chicago for their assistance.

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Authors and Affiliations

  1. Section of Plastic and Reconstructive Surgery, Departments of Surgery, Medicine and Organismal Biology, Institute for Molecular Engineering, The University of Chicago, Chicago, IL, 60637, USA

    Hannes Prescher, Michelle Ling & Raphael C. Lee

  2. Director, Laboratory for Molecular Regeneration, Department of Surgery, The University of Chicago, Chicago, IL, 60637, USA

    Raphael C. Lee

Authors
  1. Hannes Prescher
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  2. Michelle Ling
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  3. Raphael C. Lee
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Contributions

All authors whose names appear on the submission contributed to the study conception, design, data analysis, and preparation of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Raphael C. Lee.

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The authors declare that they have no conflicts of interests.

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The ethics governing the use and conduct of experiments on animals were strictly observed and the experimental protocol was approved by the University of Chicago Institutional Animal Care and Use Committee.

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Prescher, H., Ling, M. & Lee, R.C. Copolymer Surfactant Poloxamer 188 Accelerates Post-axonotemetic Sciatic Nerve Regeneration. Regen. Eng. Transl. Med. 7, 516–523 (2021). https://doi.org/10.1007/s40883-020-00174-y

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  • DOI: https://doi.org/10.1007/s40883-020-00174-y

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