Source Paper
Source Paper
D. H. Hwang, H. Y. Shin, M. J. Kwon, J. Y. Choi, B.-Y. Ryu et al.
Journal of Neuroscience • 2014
Combining cell transplantation with activity-based rehabilitation is a promising therapeutic approach for spinal cord repair. The present study was designed to investigate potential interactions between the transplantation (TP) of neural stem cells (NSCs) obtained at embryonic day 14 and treadmill training (TMT) in promoting locomotor recovery and structural repair in rat contusive injury model. Combination of TMT with NSC TP at 1 week after injury synergistically improved locomotor function. We report here that combining TMT increased the survival of grafted NSCs by >3-fold and >5-fold at 3 and 9 weeks after injury, respectively. The number of surviving NSCs was significantly correlated with the extent of locomotor recovery. NSCs grafted into the injured spinal cord were under cellular stresses induced by reactive nitrogen or oxygen species, which were markedly attenuated by TMT. TMT increased the concentration of insulin-like growth factor-1 (IGF-1) in the CSF. Intrathecal infusion of neutralizing IGF-1 antibodies, but not antibodies against either BDNF or Neurotrophin-3 (NT-3), abolished the enhanced survival of NSC grafts by TMT. The combination of TP and TMT also resulted in tissue sparing, increased myelination, and restoration of serotonergic fiber innervation to the lumbar spinal cord to a larger extent than that induced by either TP or TMT alone. Therefore, we have discovered unanticipated beneficial effects of TMT in modulating the survival of grafted NSCs via IGF-1. Our study identifies a novel neurobiological basis for complementing NSC-based spinal cord repair with activity-based neurorehabilitative approaches.
Objective: To investigate potential interactions between neural stem cell transplantation and treadmill training in promoting locomotor recovery and structural repair in a rat contusive spinal cord injury model
This is a Treadmill Locomotor Training protocol using rat as the model organism. The procedure involves 12 procedural steps, 1 equipment items, 4 materials. Extracted from a 2014 paper published in Journal of Neuroscience.
Model and subjects
rat • Not specified in provided text • unknown • Not specified in provided text • Not specified in provided text
Study window
~9 week study window
Core workflow
Spinal cord injury induction • Neural stem cell transplantation • Treadmill locomotor training
Primary readouts
Key equipment and reagents
Verified items
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Create contusive spinal cord injury in rats
Note: Baseline timepoint for subsequent interventions
“rat contusive injury model”
Transplant neural stem cells obtained at embryonic day 14 into the injured spinal cord
Note: Timing is critical - performed at 1 week post-injury
“Combination of TMT with NSC TP at 1 week after injury synergistically improved locomotor function”
Initiate treadmill training to promote locomotor recovery
Note: Combined with NSC transplantation for synergistic effects
“Combination of TMT with NSC TP at 1 week after injury synergistically improved locomotor function”
Evaluate survival of grafted neural stem cells at multiple timepoints
Note: TMT increased NSC survival by >3-fold at 3 weeks and >5-fold at 9 weeks
“combining TMT increased the survival of grafted NSCs by >3-fold and >5-fold at 3 and 9 weeks after injury, respectively”
Quantify insulin-like growth factor-1 levels in cerebrospinal fluid
Note: TMT increased IGF-1 concentration in CSF
“TMT increased the concentration of insulin-like growth factor-1 (IGF-1) in the CSF”
Administer neutralizing IGF-1 antibodies via intrathecal infusion to block IGF-1 signaling
Note: This treatment abolished the enhanced survival of NSC grafts by TMT
“Intrathecal infusion of neutralizing IGF-1 antibodies, but not antibodies against either BDNF or Neurotrophin-3 (NT-3), abolished the enhanced survival of NSC grafts by TMT”
Administer control antibodies (BDNF or NT-3) via intrathecal infusion as negative controls
Note: Control antibodies did not abolish enhanced NSC survival by TMT
“Intrathecal infusion of neutralizing IGF-1 antibodies, but not antibodies against either BDNF or Neurotrophin-3 (NT-3), abolished the enhanced survival of NSC grafts by TMT”
Evaluate reactive nitrogen or oxygen species in grafted NSCs
Note: Cellular stresses were markedly attenuated by TMT
“NSCs grafted into the injured spinal cord were under cellular stresses induced by reactive nitrogen or oxygen species, which were markedly attenuated by TMT”
Measure locomotor function recovery in treated animals
Note: Number of surviving NSCs was significantly correlated with extent of locomotor recovery
“The number of surviving NSCs was significantly correlated with the extent of locomotor recovery”
Evaluate tissue preservation in the injured spinal cord
Note: Combination of TP and TMT resulted in tissue sparing to larger extent than either alone
“The combination of TP and TMT also resulted in tissue sparing, increased myelination, and restoration of serotonergic fiber innervation”
Evaluate myelination in the injured spinal cord
Note: Increased myelination observed with combination treatment
“The combination of TP and TMT also resulted in tissue sparing, increased myelination, and restoration of serotonergic fiber innervation”
Evaluate restoration of serotonergic fiber innervation to the lumbar spinal cord
Note: Restoration was greater with combination treatment than either treatment alone
“The combination of TP and TMT also resulted in tissue sparing, increased myelination, and restoration of serotonergic fiber innervation to the lumbar spinal cord to a larger extent than that induced by either TP or TMT alone”
This section explains what the experiment is doing, which readouts matter, what the data artifacts usually look like, and how the analysis should flow from raw capture to reported result.
To investigate potential interactions between neural stem cell transplantation and treadmill training in promoting locomotor recovery and structural repair in a rat contusive spinal cord injury model
Objective
To investigate potential interactions between neural stem cell transplantation and treadmill training in promoting locomotor recovery and structural repair in a rat contusive spinal cord injury model
Subjects
From paperrat • Not specified in provided text • unknown • Not specified in provided text • Not specified in provided text
Cohort notes
From paperContusive spinal cord injury model used
Spinal cord injury induction (Not specified)
Neural stem cell transplantation (1 week after injury)
Treadmill locomotor training (Not specified)
Assessment of NSC survival (3 weeks and 9 weeks after injury)
Survival of grafted neural stem cells (at 3 and 9 weeks post-injury)
From paperNot specified in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Locomotor function recovery
From paperNot specified in provided text
Artifact type
Longitudinal gait metrics and per-animal performance tables
Comparison focus
Compare recovery trajectory across post-injury timepoints and treatment conditions
Cerebrospinal fluid IGF-1 concentration
From paperNot specified in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Cellular stress markers (reactive nitrogen and oxygen species)
From paperNot specified in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Survival of grafted neural stem cells (at 3 and 9 weeks post-injury)
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Locomotor function recovery
From paperRaw artifact
Per-run gait capture with paw placement, timing, and stride features for each animal
Processed artifact
Cleaned gait metrics table and recovery trend summary across timepoints
Final reported form
Group comparisons of gait indices, stride metrics, or recovery curves
Cerebrospinal fluid IGF-1 concentration
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Cellular stress markers (reactive nitrogen and oxygen species)
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
Preprocessing / cleaning
Not specified in provided text
Scoring or quantification
Quantify the primary readouts for this experiment: Survival of grafted neural stem cells (at 3 and 9 weeks post-injury); Locomotor function recovery; Cerebrospinal fluid IGF-1 concentration; Cellular stress markers (reactive nitrogen and oxygen species).
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Survival of grafted neural stem cells (at 3 and 9 weeks post-injury), Locomotor function recovery, Cerebrospinal fluid IGF-1 concentration, Cellular stress markers (reactive nitrogen and oxygen species).
Source links and direct wording from the methods section for validation and deeper review.
Citation
D. H. Hwang et al. (2014). Survival of Neural Stem Cell Grafts in the Lesioned Spinal Cord Is Enhanced by a Combination of Treadmill Locomotor Training via Insulin-Like Growth Factor-1 Signaling. Journal of Neuroscience
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