MicroRNA-155 Deficiency Suppresses Th17 Cell Differentiation and Improves Locomotor Recovery after Spinal Cord Injury

Tonic or phasic electrical epidural stimulation of the lumbosacral region of the spinal cord facilitates locomotion and standing in a variety of preclinical models with severe spinal cord injury. However, the mechanisms of epidural electrical stimulation that facilitate sensorimotor functions remain largely unknown. This review aims to address how epidural electrical stimulation interacts with spinal sensorimotor circuits and discusses the limitations that currently restrict the clinical implementation of this promising therapeutic approach.

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Lack of adenylate cyclase 1 (AC1): Consequences on corticospinal tract development and on locomotor recovery after spinal cord injury

Brain Research ◽

10.1016/j.brainres.2014.01.001 ◽

2014 ◽

Vol 1549 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

H. Nait Taleb Ali ◽

M.P. Morel ◽

M. Doulazmi ◽

S. Scotto-Lomassese ◽

P. Gaspar ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Adenylate Cyclase ◽

Corticospinal Tract ◽

Locomotor Recovery ◽

Cord Injury

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Oscillating field stimulation promotes axon regeneration and locomotor recovery after spinal cord injury

Neural Regeneration Research ◽

10.4103/1673-5374.327349 ◽

2022 ◽

Vol 17 (6) ◽

pp. 1318

Author(s):

Jin-Zhu Bai ◽

Yi-Xin Wang ◽

Zhen Lyu ◽

Guang-Hao Zhang ◽

Xiao-Lin Huo

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Axon Regeneration ◽

Field Stimulation ◽

Locomotor Recovery ◽

Cord Injury

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Inhibition of x-irradiation–enhanced locomotor recovery after spinal cord injury by hyperbaric oxygen or the antioxidant nitroxide tempol

Journal of Neurosurgery Spine ◽

10.3171/spi.2007.6.4.9 ◽

2007 ◽

Vol 6 (4) ◽

pp. 337-343 ◽

Cited By ~ 7

Author(s):

Virany H. Hillard ◽

Hong Peng ◽

Kaushik Das ◽

Raj Murali ◽

Chitti R. Moorthy ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Hyperbaric Oxygen ◽

Spinal Cord Tissue ◽

Irradiation Site ◽

Injury Site ◽

Locomotor Recovery ◽

Locomotor Function ◽

Cord Injury ◽

X Irradiation

Object Hyperbaric oxygen (HBO), the nitroxide antioxidant tempol, and x-irradiation have been used to promote locomotor recovery in experimental models of spinal cord injury. The authors used x-irradiation of the injury site together with either HBO or tempol to determine whether combined therapy offers greater benefit to rats. Methods Contusion injury was produced with a weight-drop device in rats at the T-10 level, and recovery was determined using the 21-point Basso-Beattie-Bresnahan (BBB) locomotor scale. Locomotor function recovered progressively during the 6-week postinjury observation period and was significantly greater after x-irradiation (20 Gy) of the injury site or treatment with tempol (275 mg/kg intraperitoneally) than in untreated rats (final BBB Scores 10.6 [x-irradiation treated] and 9.1 [tempol treated] compared with 6.4 [untreated], p < 0.05). Recovery was not significantly improved by HBO (2 atm for 1 hour [BBB Score 8.2, p > 0.05]). Interestingly, the improved recovery of locomotor function after x-irradiation, in contrast with antiproliferative radiotherapy for neoplasia, was inhibited when used together with either HBO or tempol (BBB Scores 8.2 and 8.3, respectively). The ability of tempol to block enhanced locomotor recovery by x-irradiation was accompanied by prevention of alopecia at the irradiation site. The extent of locomotor recovery following treatment with tempol, HBO, and x-irradiation correlated with measurements of spared spinal cord tissue at the contusion epicenter. Conclusions These results suggest that these treatments, when used alone, can activate neuroprotective mechanisms but, in combination, may result in neurotoxicity.

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Descending motor circuitry required for NT-3 mediated locomotor recovery after spinal cord injury in mice

Nature Communications ◽

10.1038/s41467-019-13854-3 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 6

Author(s):

Qi Han ◽

Josue D. Ordaz ◽

Nai-Kui Liu ◽

Zoe Richardson ◽

Wei Wu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Neurons ◽

Enhanced Recovery ◽

Neural Pathways ◽

Locomotor Recovery ◽

Neurotrophin 3 ◽

Cord Injury ◽

Dendritic Atrophy ◽

Descending Projections

AbstractLocomotor function, mediated by lumbar neural circuitry, is modulated by descending spinal pathways. Spinal cord injury (SCI) interrupts descending projections and denervates lumbar motor neurons (MNs). We previously reported that retrogradely transported neurotrophin-3 (NT-3) to lumbar MNs attenuated SCI-induced lumbar MN dendritic atrophy and enabled functional recovery after a rostral thoracic contusion. Here we functionally dissected the role of descending neural pathways in response to NT-3-mediated recovery after a T9 contusive SCI in mice. We find that residual projections to lumbar MNs are required to produce leg movements after SCI. Next, we show that the spared descending propriospinal pathway, rather than other pathways (including the corticospinal, rubrospinal, serotonergic, and dopaminergic pathways), accounts for NT-3-enhanced recovery. Lastly, we show that NT-3 induced propriospino-MN circuit reorganization after the T9 contusion via promotion of dendritic regrowth rather than prevention of dendritic atrophy.

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A brief period of moderate noxious stimulation induces hemorrhage and impairs locomotor recovery after spinal cord injury

Physiology & Behavior ◽

10.1016/j.physbeh.2019.112695 ◽

2019 ◽

Vol 212 ◽

pp. 112695 ◽

Cited By ~ 3

Author(s):

Misty M. Strain ◽

Michelle A. Hook ◽

Joshua D. Reynolds ◽

Yung-Jen Huang ◽

Melissa K. Henwood ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Noxious Stimulation ◽

Locomotor Recovery ◽

Cord Injury

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CCL3 contributes to secondary damage after spinal cord injury

Journal of Neuroinflammation ◽

10.1186/s12974-020-02037-3 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Nicolas Pelisch ◽

Jose Rosas Almanza ◽

Kyle E. Stehlik ◽

Brandy V. Aperi ◽

Antje Kroner

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Inflammatory Response ◽

Lesion Size ◽

Secondary Injury ◽

Wild Type ◽

Locomotor Recovery ◽

Secondary Damage ◽

Cord Injury

Abstract Background Secondary damage after spinal cord injury (SCI) is characterized by a cascade of events including hemorrhage, apoptosis, oxidative stress, and inflammation which increase the lesion size which can influence the functional impairment. Thus, identifying specific mechanisms attributed to secondary injury is critical in minimizing tissue damage and improving neurological outcome. In this work, we are investigating the role of CCL3 (macrophage inflammatory protein 1-α, MIP-1α), a chemokine involved in the recruitment of inflammatory cells, which plays an important role in inflammatory conditions of the central and peripheral nervous system. Methods A mouse model of lower thoracic (T11) spinal cord contusion injury was used. We assessed expression levels of CCL3 and its receptors on the mRNA and protein level and analyzed changes in locomotor recovery and the inflammatory response in the injured spinal cord of wild-type and CCL3−/− mice. Results The expression of CCL3 and its receptors was increased after thoracic contusion SCI in mice. We then examined the role of CCL3 after SCI and its direct influence on the inflammatory response, locomotor recovery and lesion size using CCL3−/− mice. CCL3−/− mice showed mild but significant improvement of locomotor recovery, a smaller lesion size and reduced neuronal damage compared to wild-type controls. In addition, neutrophil numbers as well as the pro-inflammatory cytokines and chemokines, known to play a deleterious role after SCI, were markedly reduced in the absence of CCL3. Conclusion We have identified CCL3 as a potential target to modulate the inflammatory response and secondary damage after SCI. Collectively, this study shows that CCL3 contributes to progressive tissue damage and functional impairment during secondary injury after SCI.

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CCR5 Blockade Promotes M2 Macrophage Activation and Improves Locomotor Recovery After Spinal Cord Injury in Mice

Inflammation ◽

10.1007/s10753-014-0014-z ◽

2014 ◽

Vol 38 (1) ◽

pp. 126-133 ◽

Cited By ~ 17

Author(s):

Fengtao Li ◽

Bin Cheng ◽

Jian Cheng ◽

Dong Wang ◽

Haopeng Li ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Macrophage Activation ◽

M2 Macrophage ◽

Locomotor Recovery ◽

Cord Injury ◽

Ccr5 Blockade

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Treadmill training promotes spinal changes leading to locomotor recovery after partial spinal cord injury in cats

Journal of Neurophysiology ◽

10.1152/jn.01044.2012 ◽

2013 ◽

Vol 109 (12) ◽

pp. 2909-2922 ◽

Cited By ~ 31

Author(s):

Marina Martinez ◽

Hugo Delivet-Mongrain ◽

Serge Rossignol

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Treadmill Training ◽

Locomotor Training ◽

Locomotor Recovery ◽

Thoracic Level ◽

Spinal Circuitry ◽

Cord Injury ◽

Locomotor Deficits ◽

Spinal Hemisection

After a spinal hemisection at thoracic level in cats, the paretic hindlimb progressively recovers locomotion without treadmill training but asymmetries between hindlimbs persist for several weeks and can be seen even after a further complete spinal transection at T13. To promote optimal locomotor recovery after hemisection, such asymmetrical changes need to be corrected. In the present study we determined if the locomotor deficits induced by a spinal hemisection can be corrected by locomotor training and, if so, whether the spinal stepping after the complete spinal cord transection is also more symmetrical. This would indicate that locomotor training in the hemisected period induces efficient changes in the spinal cord itself. Sixteen adult cats were first submitted to a spinal hemisection at T10. One group received 3 wk of treadmill training, whereas the second group did not. Detailed kinematic and electromyographic analyses showed that a 3-wk period of locomotor training was sufficient to improve the quality and symmetry of walking of the hindlimbs. Moreover, after the complete spinal lesion was performed, all the trained cats reexpressed bilateral and symmetrical hindlimb locomotion within 24 h. By contrast, the locomotor pattern of the untrained cats remained asymmetrical, and the hindlimb on the side of the hemisection was still deficient. This study highlights the beneficial role of locomotor training in facilitating bilateral and symmetrical functional plastic changes within the spinal circuitry and in promoting locomotor recovery after an incomplete spinal cord injury.

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