Molecular and Cellular Changes in the Lumbar Spinal Cord following Thoracic Injury: Regulation by Treadmill Locomotor Training

Background. We previously demonstrated that step training leads to reorganization of neuronal networks in the lumbar spinal cord of rodents after a hemisection (HX) injury and step training, including increases excitability of spinally evoked potentials in hindlimb motor neurons. Methods. In this study, we investigated changes in RNA expression and synapse number using RNA-Seq and immunohistochemistry of the lumbar spinal cord 23 days after a mid-thoracic HX in rats with and without post-HX step training. Results. Gene Ontology (GO) term clustering demonstrated that expression levels of 36 synapse-related genes were increased in trained compared with nontrained rats. Many synaptic genes were upregulated in trained rats, but Lrrc4 (coding NGL-2) was the most highly expressed in the lumbar spinal cord caudal to the HX lesion. Trained rats also had a higher number of NGL-2/synaptophysin synaptic puncta in the lumbar ventral horn. Conclusions. Our findings demonstrate clear activity-dependent regulation of synapse-related gene expression post-HX. This effect is consistent with the concept that activity-dependent phenomena can provide a mechanistic drive for epigenetic neuronal group selection in the shaping of the reorganization of synaptic networks to learn the locomotion task being trained after spinal cord injury.

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Effects of Rehabilitation on Perineural Nets and Synaptic Plasticity Following Spinal Cord Transection

Brain Sciences ◽

10.3390/brainsci10110824 ◽

2020 ◽

Vol 10 (11) ◽

pp. 824

Author(s):

Yazi D. Al’joboori ◽

V. Reggie Edgerton ◽

Ronaldo M. Ichiyama

Keyword(s):

Spinal Cord ◽

Synaptic Plasticity ◽

Lumbar Spinal Cord ◽

Locomotor Training ◽

Post Injury ◽

Spinal Transection ◽

Adult Rats ◽

Synaptic Changes ◽

Lumbar Spinal ◽

Functional Gain

Epidural electrical stimulation (ES) of the lumbar spinal cord combined with daily locomotor training has been demonstrated to enhance stepping ability after complete spinal transection in rodents and clinically complete spinal injuries in humans. Although functional gain is observed, plasticity mechanisms associated with such recovery remain mostly unclear. Here, we investigated how ES and locomotor training affected expression of chondroitin sulfate proteoglycans (CSPG), perineuronal nets (PNN), and synaptic plasticity on spinal motoneurons. To test this, adult rats received a complete spinal transection (T9–T10) followed by daily locomotor training performed under ES with administration of quipazine (a serotonin (5-HT) agonist) starting 7 days post-injury (dpi). Excitatory and inhibitory synaptic changes were examined at 7, 21, and 67 dpi in addition to PNN and CSPG expression. The total amount of CSPG expression significantly increased with time after injury, with no effect of training. An interesting finding was that γ-motoneurons did not express PNNs, whereas α-motoneurons demonstrated well-defined PNNs. This remarkable difference is reflected in the greater extent of synaptic changes observed in γ-motoneurons compared to α-motoneurons. A medium negative correlation between CSPG expression and changes in putative synapses around α-motoneurons was found, but no correlation was identified for γ-motoneurons. These results suggest that modulation of γ-motoneuron activity is an important mechanism associated with functional recovery induced by locomotor training under ES after a complete spinal transection.

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Lipomeningocele associated with diplomyelia in a dog

Tierärztliche Praxis Ausgabe K Kleintiere / Heimtiere ◽

10.15654/tpk-170751 ◽

2018 ◽

Vol 46 (05) ◽

pp. 323-329 ◽

Cited By ~ 2

Author(s):

Nele Ondreka ◽

Sara Malberg ◽

Emma Laws ◽

Martin Schmidt ◽

Sabine Schulze

Keyword(s):

Spinal Cord ◽

Neurological Status ◽

Split Cord Malformation ◽

Lumbar Spinal Cord ◽

Histopathological Diagnosis ◽

Type I ◽

Thoracic Spinal Cord ◽

Thoracic Spinal ◽

Subcutaneous Mass ◽

Lumbar Spinal

SummaryA 2-year-old male neutered mixed breed dog with a body weight of 30 kg was presented for evaluation of a soft subcutaneous mass on the dorsal midline at the level of the caudal thoracic spine. A further clinical sign was intermittent pain on palpation of the area of the subcutaneous mass. The owner also described a prolonged phase of urination with repeated interruption and re-initiation of voiding. The findings of the neurological examination were consistent with a lesion localization between the 3rd thoracic and 3rd lumbar spinal cord segments. Magnetic resonance imaging revealed a spina bifida with a lipomeningocele and diplomyelia (split cord malformation type I) at the level of thoracic vertebra 11 and 12 and secondary syringomyelia above the aforementioned defects in the caudal thoracic spinal cord. Surgical resection of the lipomeningocele via a hemilaminectomy was performed. After initial deterioration of the neurological status postsurgery with paraplegia and absent deep pain sensation the dog improved within 2 weeks to non-ambulatory paraparesis with voluntary urination. Six weeks postoperatively the dog was ambulatory, according to the owner. Two years after surgery the owner recorded that the dog showed a normal gait, a normal urination and no pain. Histopathological diagnosis of the biopsied material revealed a lipomeningocele which confirmed the radiological diagnosis.

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Faculty Opinions recommendation of Functional organization of locomotor interneurons in the ventral lumbar spinal cord of the newborn rat.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13601956.14995056 ◽

2012 ◽

Author(s):

Serge Rossignol

Keyword(s):

Spinal Cord ◽

Functional Organization ◽

Lumbar Spinal Cord ◽

Newborn Rat ◽

Lumbar Spinal

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Faculty Opinions recommendation of Neurologic improvement after thoracic, thoracolumbar, and lumbar spinal cord (conus medullaris) injuries.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.8263956.8692054 ◽

2011 ◽

Author(s):

Carlos Bagley

Keyword(s):

Spinal Cord ◽

Conus Medullaris ◽

Lumbar Spinal Cord ◽

Lumbar Spinal

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Aging process of the human lumbar spinal cord: A morphometric analysis

Neuropathology ◽

10.1111/j.1440-1789.1996.tb00164.x ◽

1996 ◽

Vol 16 (2) ◽

pp. 106-111 ◽

Cited By ~ 5

Author(s):

Ming Zhou ◽

Noboru Goto ◽

Chen Zhang ◽

Wei Tang

Keyword(s):

Spinal Cord ◽

Morphometric Analysis ◽

Aging Process ◽

Lumbar Spinal Cord ◽

Lumbar Spinal

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Multi-pronged neuromodulation intervention engages the residual motor circuitry to facilitate walking in a rat model of spinal cord injury

Nature Communications ◽

10.1038/s41467-021-22137-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Marco Bonizzato ◽

Nicholas D. James ◽

Galyna Pidpruzhnykova ◽

Natalia Pavlova ◽

Polina Shkorbatova ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Rat Model ◽

Stress Responses ◽

Learning Algorithm ◽

Lumbar Spinal Cord ◽

Cord Injury ◽

Potential Synergy ◽

Lumbar Spinal ◽

Deep Brain

AbstractA spinal cord injury usually spares some components of the locomotor circuitry. Deep brain stimulation (DBS) of the midbrain locomotor region and epidural electrical stimulation of the lumbar spinal cord (EES) are being used to tap into this spared circuitry to enable locomotion in humans with spinal cord injury. While appealing, the potential synergy between DBS and EES remains unknown. Here, we report the synergistic facilitation of locomotion when DBS is combined with EES in a rat model of severe contusion spinal cord injury leading to leg paralysis. However, this synergy requires high amplitudes of DBS, which triggers forced locomotion associated with stress responses. To suppress these undesired responses, we link DBS to the intention to walk, decoded from cortical activity using a robust, rapidly calibrated unsupervised learning algorithm. This contingency amplifies the supraspinal descending command while empowering the rats into volitional walking. However, the resulting improvements may not outweigh the complex technological framework necessary to establish viable therapeutic conditions.

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