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

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.

SUBMITTER: Siddiqui AM

PROVIDER: S-EPMC8528837 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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

Siddiqui Ahad M AM Islam Riazul R Cuellar Carlos A CA Silvernail Jodi L JL Knudsen Bruce B Curley Dallece E DE Strickland Tammy T Manske Emilee E Suwan Parita T PT Latypov Timur T Akhmetov Nafis N Zhang Shuya S Summer Priska P Nesbitt Jarred J JJ Chen Bingkun K BK Grahn Peter J PJ Madigan Nicolas N NN Yaszemski Michael J MJ Windebank Anthony J AJ Lavrov Igor A IA

NPJ Regenerative medicine 20211020 1

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 E ...[more]

PMID: 34671050

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Project description:Spontaneous, acute, complete thoracolumbar spinal cord injury (TL-SCI) in dogs frequently results in permanent deficits modeling chronic paralysis in people. Recovery of walking without recovery of sensation has been interpreted in dogs as reflexive spinal walking. To evaluate this assumption, this study characterized the electrophysiological status of motor and sensory long tracts and local reflex circuitry in dogs with absent recovery of sensation after acute TL-SCI and correlated findings to gait scores. Twenty dogs with permanent deficits after acute, clinically complete TL-SCI and 6 normal dogs were prospectively enrolled. Transcranial magnetic motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs), H-reflex, and F-waves were evaluated. Gait was quantified using an ordinal, open field scale (OFS) and treadmill-based stepping and coordination scores (SS, RI). MEP latency and H-reflex variables were compared between cases and controls. Associations between presence of MEPs, SSEPs, F-waves or H-reflex variables, and gait scores were determined. Pelvic limb MEPs were detected in 4 cases; no case had trans-lesional sensory conduction. Latency was longer and conduction velocity slower in cases than controls (pa = 0.0064, 0.0023, respectively). Three of 4 cases with pelvic limb MEPs were ambulatory, and gait scores (OFS, SS, RI) were each associated with presence of trans-lesional conduction (pa = 0.006, 0.006, 0.003, respectively). H threshold in cases (mean, 3.2mA ±2.5) was lower than controls (mean, 7.9mA ±3.1; pa = 0.011) and was inversely associated with treadmill-based scores, SS, and RI (pa = 0.042, 0.043, respectively). The association between pelvic limb MEPs and gait scores supports the importance of descending influence on regaining walking after severe TL-SCI in dogs rather than just activation of spinal walking. The inverse association between H-reflex threshold and gait scores implies that increases in motor neuron pool excitability might also contribute to motor recovery.

Dataset Information

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

Publications

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

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