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

2020 ◽  
Vol 10 (11) ◽  
pp. 824
Author(s):  
Yazi D. Al’joboori ◽  
V. Reggie Edgerton ◽  
Ronaldo M. Ichiyama

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.

2019 ◽  
Vol 33 (3) ◽  
pp. 225-231 ◽  
Author(s):  
Kazu Kobayakawa ◽  
Kyleigh Alexis DePetro ◽  
Hui Zhong ◽  
Bau Pham ◽  
Masamitsu Hara ◽  
...  

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.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2025 ◽  
Author(s):  
Qinfeng Wu ◽  
Yana Cao ◽  
Chuanming Dong ◽  
Hongxing Wang ◽  
Qinghua Wang ◽  
...  

Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training retained hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery.


2021 ◽  
Vol 22 (11) ◽  
pp. 6007
Author(s):  
Urszula Sławińska ◽  
Henryk Majczyński ◽  
Anna Kwaśniewska ◽  
Krzysztof Miazga ◽  
Anna M. Cabaj ◽  
...  

Coordination of four-limb movements during quadrupedal locomotion is controlled by supraspinal monoaminergic descending pathways, among which serotoninergic ones play a crucial role. Here we investigated the locomotor pattern during recovery from blockade of 5-HT7 or 5-HT2A receptors after intrathecal application of SB269970 or cyproheptadine in adult rats with chronic intrathecal cannula implanted in the lumbar spinal cord. The interlimb coordination was investigated based on electromyographic activity recorded from selected fore- and hindlimb muscles during rat locomotion on a treadmill. In the time of recovery after hindlimb transient paralysis, we noticed a presence of an unusual pattern of quadrupedal locomotion characterized by a doubling of forelimb stepping in relation to unaffected hindlimb stepping (2FL-1HL) after blockade of 5-HT7 receptors but not after blockade of 5-HT2A receptors. The 2FL-1HL pattern, although transient, was observed as a stable form of fore-hindlimb coupling during quadrupedal locomotion. We suggest that modulation of the 5-HT7 receptors on interneurons located in lamina VII with ascending projections to the forelimb spinal network can be responsible for the 2FL-1HL locomotor pattern. In support, our immunohistochemical analysis of the lumbar spinal cord demonstrated the presence of the 5-HT7 immunoreactive cells in the lamina VII, which were rarely 5-HT2A immunoreactive.


2019 ◽  
Vol 122 (2) ◽  
pp. 585-600 ◽  
Author(s):  
Yury Gerasimenko ◽  
Chet Preston ◽  
Hui Zhong ◽  
Roland R. Roy ◽  
V. Reggie Edgerton ◽  
...  

The precise location and functional organization of the spinal neuronal locomotor-related networks in adult mammals remain unclear. Our recent neurophysiological findings provided empirical evidence that the rostral lumbar spinal cord segments play a critical role in the initiation and generation of the rhythmic activation patterns necessary for hindlimb locomotion in adult spinal rats. Since added epidural stimulation at the S1 segments significantly enhanced the motor output generated by L2 stimulation, these data also suggested that the sacral spinal cord provides a strong facilitory influence in rhythm initiation and generation. However, whether L2 will initiate hindlimb locomotion in the absence of S1 segments, and whether S1 segments can facilitate locomotion in the absence of L2 segments remain unknown. Herein, adult rats received complete spinal cord transections at T8 and then at either L2 or S1. Rats with spinal cord transections at T8 and S1 remained capable of generating coordinated hindlimb locomotion when receiving epidural stimulation at L2 and when ensembles of locomotor related loadbearing input were present. In contrast, minimal locomotion was observed when S1 stimulation was delivered after spinal cord transections at T8 and L2. Results were similar when the nonspecific serotonergic agonists were administered. These results demonstrate in adult rats that rostral lumbar segments are essential for the regulation of hindlimb locomotor rhythmicity. In addition, the more caudal spinal networks alone cannot control locomotion in the absence of the rostral segments around L2 even when loadbearing rhythmic proprioceptive afferent input is imposed. NEW & NOTEWORTHY The exact location of the spinal neuronal locomotor-related networks in adult mammals remains unknown. The present data demonstrate that when the rostral lumbar spinal segments (~L2) are completely eliminated in thoracic spinal adult rats, hindlimb stepping is not possible with neurochemical modulation of the lumbosacral cord. In contrast, eliminating the sacral cord retains stepping ability. These observations highlight the importance of rostral lumbar segments in generating effective mammalian locomotion.


PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e88215 ◽  
Author(s):  
Hae Young Shin ◽  
Hyosil Kim ◽  
Min Jung Kwon ◽  
Dong Hoon Hwang ◽  
KiYoung Lee ◽  
...  

2018 ◽  
Vol 46 (05) ◽  
pp. 323-329 ◽  
Author(s):  
Nele Ondreka ◽  
Sara Malberg ◽  
Emma Laws ◽  
Martin Schmidt ◽  
Sabine Schulze

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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