Newly regenerated axons via scaffolds promote sub-lesional reorganization and motor recovery with epidural electrical stimulation

Ahad M. Siddiqui, Riazul Islam, Carlos A. Cuellar, Jodi L. Silvernail, Bruce Knudsen, Dallece E. Curley, Tammy Strickland, Emilee Manske, Parita T. Suwan, Timur Latypov, Nafis Akhmetov, Shuya Zhang, Priska Summer, Jarred J. Nesbitt, Bingkun K. Chen, Peter J. Grahn, Nicolas N. Madigan, Michael J. Yaszemski, Anthony J. Windebank, Igor A. Lavrov

Research output: Contribution to journalArticlepeer-review

Abstract

Here, we report the effect of newly regenerated axons via scaffolds on reorganization of spinal circuitry and restoration of motor functions with epidural electrical stimulation (EES). Motor recovery was evaluated for 7 weeks after spinal transection and following implantation with scaffolds seeded with neurotrophin producing Schwann cell and with rapamycin microspheres. Combined treatment with scaffolds and EES-enabled stepping led to functional improvement compared to groups with scaffold or EES, although, the number of axons across scaffolds was not different between groups. Re-transection through the scaffold at week 6 reduced EES-enabled stepping, still demonstrating better performance compared to the other groups. Greater synaptic reorganization in the presence of regenerated axons was found in group with combined therapy. These findings suggest that newly regenerated axons through cell-containing scaffolds with EES-enabled motor training reorganize the sub-lesional circuitry improving motor recovery, demonstrating that neuroregenerative and neuromodulatory therapies cumulatively enhancing motor function after complete SCI.

Original languageEnglish (US)
Article number66
Journalnpj Regenerative Medicine
Volume6
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Developmental Biology
  • Cell Biology

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