scholarly journals Molecular mechanisms underlying the positive role of treadmill training in locomotor recovery after spinal cord injury

Spinal Cord ◽  
2016 ◽  
Vol 55 (5) ◽  
pp. 441-446 ◽  
Author(s):  
Q Liu ◽  
B Zhang ◽  
C Liu ◽  
D Zhao
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Molecular Mechanisms ◽  
Treadmill Training ◽  
Positive Role ◽  
Locomotor Recovery ◽  
Cord Injury

scholarly journals CCL3 contributes to secondary damage after spinal cord injury

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.

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

2013 ◽  
Vol 109 (12) ◽  
pp. 2909-2922 ◽  
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.

Treadmill training based on the overload principle promotes locomotor recovery in a mouse model of chronic spinal cord injury

2021 ◽  
pp. 113834
Author(s):  
Takahiro Shibata ◽  
Syoichi Tashiro ◽  
Munehisa Shinozaki ◽  
Shogo Hashimoto ◽  
Morio Matsumoto ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Mouse Model ◽  
Treadmill Training ◽  
Chronic Spinal Cord Injury ◽  
Locomotor Recovery ◽  
Cord Injury

scholarly journals Acute administration of Baclofen after spinal cord injury improves locomotor behavior, bladder control and modulates the inflammatory response.

2021 ◽  
Author(s):  
Nídia de Sousa ◽  
Andreia Pinho ◽  
Susana Monteiro ◽  
Valentina Liberato ◽  
Diogo Santos ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Molecular Mechanisms ◽  
Muscle Tone ◽  
Gabab Receptors ◽  
Bladder Function ◽  
Acute Administration ◽  
Functional Impairments ◽  
Cord Injury

Spinal cord injury (SCI) leads to severe motor and sensory functional impairments that affect personal and social behaviors. With no effective treatment, deficits in motor function are the most visible consequence of SCI. However, other complications produce a significant impact on SCI patient’s welfare. Spasticity is a neurological impairment that affects the control of muscle tone as a consequence of an insult in the central nervous system (e.g., SCI). Baclofen, a GABA agonist, is the most effective drug for spasticity treatment. This drug activates GABAB receptors decreasing the neurotransmitters release and neuronal hyperpolarization, which results in spasticity relief. Interestingly, emerging data reveals that Baclofen can also play a role on neuroprotection and regeneration after SCI. Our goal is to highlight the role of Baclofen as a potential treatment to promote recovery from SCI. We used a compression SCI mouse model with the administration of Baclofen at different time-points after injury. Our data showed that Baclofen is more effective when a single dose is administered acutely, leading to locomotor improvements in mice. Moreover, Baclofen administration also led to improved bladder function control in all experimental groups. Interestingly, acute Baclofen administration modulates microglia activation state and levels of circulating cytokines, suggesting a role of Baclofen in the modulation of the immune response. Although deeper studies must be performed to understand the cellular/molecular mechanisms that underlie the functional improvements produced by Baclofen, our data shed light into the pharmacological potential of Baclofen to promote recovery in a SCI context.

scholarly journals PD-L1 Improves Motor Function and Alleviates Neuropathic Pain in Male Mice After Spinal Cord Injury by Inhibiting MAPK Pathway

2021 ◽  
Author(s):  
Jiangang Shi ◽  
FanQi Kong ◽  
Kaiqiang Sun ◽  
Jian Zhu ◽  
FuDong Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Inflammatory Response ◽  
Mapk Pathway ◽  
Expression Patterns ◽  
Motor Dysfunction ◽  
Locomotor Recovery ◽  
Cord Injury

Abstract Background Traumatic spinal cord injury (SCI) causes severe motor dysfunction and persistent central neuropathic pain (Nep) that remains uncured yet. Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and contributes to the immune-suppressive in tumor microenvironment, and the role of PD-L1 in regulating inflammatory response and Nep after SCI remains unclear. A growing amount of research has begun to investigate the effect of PD-L1 on macrophages and microglia. Considering the pivotal role of macrophages/microglia in the inflammatory response after SCI, we tested the hypothesis that PD-L1 improved the recovery of locomotor and sensory functions after SCI through macrophages and microglia. Methods The mice SCI model was employed to determine the changes in expression patterns of PD-L1. Meanwhile, we constructed PD-L1 knockout mice to observe differences in functional recovery and phenotypes of macrophages/microglia post-SCI. Results In present study, PD-L1 was significantly upregulated after SCI and highly expressed on macrophages/microglia. PD-L1 knockout (KO) mice showed poor locomotor recovery and serious pathological pain compared with wild-type (WT) mice. Furthermore, deletion of PD-L1 significantly increased the polarization of M1-like macrophages/microglia. Mechanistic analysis revealed that PD-L1 may improve functional outcomes following SCI by inhibiting phosphorylation of p38 and ERK1/2. Conclusions Our observations implicate the involvement of PD-L1 in recovery of SCI and provide a new treatment strategy for prevention and treatment of this traumatic condition.

scholarly journals CCL3 contributes to secondary damage after spinal cord injury

2020 ◽  
Author(s):  
Nicolas Pelisch ◽  
Jose Rosas Almanza ◽  
Kyle Edward 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 is 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 and a smaller lesion size 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 the absence of CCL3 can contribute to reduced tissue damage and better functional recovery during secondary injury after SCI.

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