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Exp Neurol. 2019 Feb;312:51-62. doi: 10.1016/j.expneurol.2018.11.003. Epub 2018 Nov 22.

Validation study of neurotrophin-3-releasing chitosan facilitation of neural tissue generation in the severely injured adult rat spinal cord.

Author information

1
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136-1060, United States; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, United States; Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL 33136, United States. Electronic address: moudega@miami.edu.
2
Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
3
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136-1060, United States.
4
Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Beijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration, Beijing Key Laboratory for Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.
5
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136-1060, United States; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
6
Division of Spine Surgery, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; Institute of Spine and Spine Cord Injury of Tongji University, Shanghai 200065, China; Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
7
Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; Department of Psychiatry and Biobehavioral Sciences, UCLA Medical School, Los Angeles, CA 90095, United States.

Abstract

It was previously reported that a tube holding chitosan carriers loaded with neurotrophin-3 (NT-3), after insertion into a 5 mm long transection gap in the adult rat spinal cord, triggered de novo neural tissue generation and functional recovery. Here, we report an effort to validate these findings using stringent blinding methodologies, which are crucial for robustness in reproducing biomedical studies. Radio frequency identification (RFID) chips were utilized to label rats that were randomly assigned into three experimental groups: transection with chitosan-NT-3 implant (C-NT3), transection only (T-controls), and laminectomy only (S-controls), blinding the experimenters to the treatments. Three months after surgery, animals only known by their RFID were functionally, electrophysiologically, and anatomically assessed. The data were then collected into the proper groups and statistically analyzed. Neural tissue with nestin-, Tuj1-, and NeuN-positive cells was found bridging the transection gap in C-NT3 rats, but not in T-controls. Motor- and somatosensory-evoked potentials were detected in C-NT3 rats and S-controls, but not in T-controls. Hind limb movement was significantly better in C-NT3 rats compared with T-controls. Our validation study indicates that C-NT3 implants facilitate neural tissue generation, at least in part, by eliciting endogenous neurogenesis. Our data support the use of C-NT3 implants for tissue remodeling in the injured spinal cord.

KEYWORDS:

Biomaterial; NT-3; Neurogenesis; Regeneration; Replication; Spinal cord injury

PMID:
30471251
DOI:
10.1016/j.expneurol.2018.11.003
[Indexed for MEDLINE]
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