scholarly journals Recovery of motor function of chronic spinal cord injury by extracellular pyruvate kinase isoform M2 and the underlying mechanism

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Takahiro Kikuchi ◽  
Chihiro Tohda ◽  
Masato Suyama
Keyword(s):  
Spinal Cord ◽  
Pyruvate Kinase ◽  
Motor Function ◽  
Motor Neurons ◽  
Chronic Phase ◽  
Indirect Evidence ◽  
Cord Injury ◽  
Axonal Density ◽  
Recovery Of Motor Function

Abstract In our previous study, we found that pyruvate kinase isoform M2 (PKM2) was secreted from the skeletal muscle and extended axons in the cultured neuron. Indirect evidence suggested that secreted PKM2 might relate to the recovery of motor function in spinal cord injured (SCI) mice. However, in vivo direct evidence has not been obtained, showing that extracellular PKM2 improved axonal density and motor function in SCI mice. In addition, the signal pathway of extracellular PKM2 underlying the increase in axons remained unknown. Therefore, this study aimed to identify a target molecule of extracellular PKM2 in neurons and investigate the critical involvement of extracellular PKM2 in functional recovery in the chronic phase of SCI. Recombinant PKM2 infusion to the lateral ventricle recovered motor function in the chronic phase of SCI mice. The improvement of motor function was associated with axonal increase, at least of raphespinal tracts connecting to the motor neurons directly or indirectly. Target molecules of extracellular PKM2 in neurons were identified as valosin-containing protein (VCP) by the drug affinity responsive target stability method. ATPase activation of VCP mediated the PKM2-induced axonal increase and recovery of motor function in chronic SCI related to the increase in axonal density. It is a novel finding that axonal increase and motor recovery are mediated by extracellular PKM2-VCP-driven ATPase activity.

Intrathecal Infusion of Diosgenin during the Chronic Phase of Spinal Cord Injury Ameliorates Motor Function and Axonal Density

2021 ◽  
Vol 15 (4) ◽  
pp. 454-461
Author(s):  
Aoi Nakano ◽  
Ximeng Yang ◽  
Tomoharu Kuboyama ◽  
Yuna Inada ◽  
Chihiro Tohda
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Chronic Phase ◽  
Cord Injury ◽  
Axonal Density ◽  
Intrathecal Infusion

4:40104. Experimental Distraction Spinal Cord Injury and Recovery of Motor Function

2006 ◽  
Vol 6 (5) ◽  
pp. 51S ◽  
Author(s):  
Mary K. Nagai ◽  
Kirk Dabney ◽  
Marina Ehrenshteyn ◽  
Dianna Willis ◽  
Jeffery Twiss
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Cord Injury ◽  
Recovery Of Motor Function

scholarly journals Effect of Shikonin on Spinal Cord Injury in Rats Via Regulation of HMGB1/TLR4/NF-kB Signaling Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 481-491 ◽  
Author(s):  
Yihui Bi ◽  
Yapeng Zhu ◽  
Mingkai Zhang ◽  
Keke Zhang ◽  
Xingyi Hua ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Motor Function ◽  
Tissue Repair ◽  
Underlying Mechanism ◽  
Molecular Signaling ◽  
Cord Injury

Background/Aims: Shikonin, a compound extracted from Zicao, has been demonstrated to hold anti-bacterial, anti-inflammatory, and anti-tumor activities in various diseases and it has been shown to protect human organs from injuries. However, the effect of shikonin on the recovery of spinal cord injury (SCI) remains unknown. This study was designed to estimate the potential therapeutic effect and underlying mechanism of shikonin on SCI in vivo. Methods: In the study, we used HE staining, ELISA assay, transfection assay, TUNEL assay, real time PCR and Western blot to detect the effects of shikonin on spinal cord injury in rats. Results: we showed that shikonin could promote the recovery of motor function and tissue repair after SCI treatment in rats SCI model. Moreover, we demonstrated that shikonin inhibited the spinal cord edema in SCI model of rats. According to further investigation, shikonin induced the reduction of inflammatory response through decreasing the expression levels of HMGB1, TLR4 and NF-κB after SCI injury. In addition, we also found that shikonin could suppress the apoptosis and expression of caspase-3 protein in SCI model of rats. Conclusion: Our results demonstrated that shikonin induced the recovery of tissue repair and motor function via inactivation of HMGB1/TLR4/NF-κB signaling pathway in SCI model of rats. Meanwhile, shikonin regulated the inflammation response in SCI by suppressing the HMGB1/TLR4/NF-κB signaling pathway. The described mechanism sheds novel light on molecular signaling pathway in spinal cord injury and secondary injury including inflammatory response.

scholarly journals TRIM32 affects the recovery of motor function following spinal cord injury through regulating proliferation of glia

Oncotarget ◽  
2017 ◽  
Vol 8 (28) ◽  
pp. 45380-45390 ◽  
Author(s):  
Qiang Fu ◽  
Ming-Ming Zou ◽  
Jian-Wei Zhu ◽  
Yan Zhang ◽  
Wen-Jin Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Cord Injury ◽  
Recovery Of Motor Function

Mechanisms of Behavioral Changes After Spinal Cord Injury

2019 ◽  
Author(s):  
Karim Fouad ◽  
Abel Torres-Espín ◽  
Keith K. Fenrich
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Lesion Size ◽  
Behavioral Changes ◽  
Sensory Function ◽  
Wide Range ◽  
Cord Injury ◽  
New Treatment ◽  
Recovery Of Motor Function

Spinal cord injury results in a wide range of behavioral changes including impaired motor and sensory function, autonomic dysfunction, spasticity, and depression. Currently, restoring lost motor function is the most actively studied and sought-after goal of spinal cord injury research. This research is rooted in the fact that although self-repair following spinal cord injury in adult mammals is very limited, there can be some recovery of motor function. This recovery is strongly dependent on the lesion size and location as well as on neural activity of denervated networks activated mainly through physical activity (i.e., rehabilitative training). Recovery of motor function is largely due to neuroplasticity, which includes adaptive changes in spared and injured neural circuitry. Neuroplasticity after spinal cord injury is extensive and includes mechanisms such as moderate axonal sprouting, the formation of new synaptic connections, network remapping, and changes to neuron cell properties. Neuroplasticity after spinal cord injury has been described at various physiological and anatomical levels of the central nervous system including the brain, brainstem, and spinal cord, both above and below injury sites. The growing number of mechanisms underlying postinjury plasticity indicate the vast complexity of injury-induced plasticity. This poses important opportunities to further enhance and harness plasticity in order to promote recovery. However, the diversity of neuroplasticity also creates challenges for research, which is frequently based on mechanistically driven approaches. The appreciation of the complexity of neuronal plasticity and the findings that recovery is based on a multitude and interlinked adaptations will be essential in developing meaningful new treatment avenues.

Effect of vitamins C and E on recovery of motor function after spinal cord injury: systematic review and meta-analysis of animal studies

2019 ◽  
Vol 78 (6) ◽  
pp. 465-473 ◽  
Author(s):  
Mostafa Hosseini ◽  
Arash Sarveazad ◽  
Asrin Babahajian ◽  
Masoud Baikpour ◽  
Alexander R Vaccaro ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Vitamin E ◽  
Animal Models ◽  
Vitamin C ◽  
Motor Function ◽  
Animal Studies ◽  
Meta Analysis ◽  
Cord Injury ◽  
Recovery Of Motor Function

Abstract Context Many animal studies have evaluated the role of vitamins in the recovery of motor function after spinal cord injury, but their results have been contradictory and no consensus has been reached. Objective This meta-analysis aimed to investigate the effects of vitamin C and vitamin E on recovery of motor function after spinal cord injury in animal models. Data Sources Two authors independently collected the records of relevant articles published in MEDLINE, Embase, Scopus, and Web of Science through November 2018. Study Selection All studies conducted in animal models to evaluate the therapeutic effects of vitamin C or vitamin E or both on recovery of motor function after spinal cord injury were included. Studies that lacked a control group or a standard treatment, lacked an assessment of motor function, included genetically modified/engineered animals, included animals pretreated with vitamin C or vitamin E, or combined vitamin treatment with other methods, such as cell therapies, were excluded. Data Extraction Data from 10 articles met the inclusion criteria for meta-analysis, conducted in accordance with PRISMA guidelines. Results Daily supplementation with vitamin C (P < 0.0001) and vitamin E (P < 0.0001) significantly improved the recovery of motor function in animals affected by spinal cord injury. Vitamin C supplementation is effective only when administered intraperitoneally (P < 0.0001). Concurrent supplementation with both vitamins does not show better efficacy than treatment with either one alone. Conclusion Administration of vitamin C and vitamin E in animal models of spinal cord injury significantly improves the recovery of motor function.

scholarly journals Effects of repetitive magnetic stimulation on motor function and GAP43 and 5-HT expression in rats with spinal cord injury

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052097076
Author(s):  
Hao Liu ◽  
Deqi Xiong ◽  
Rizhao Pang ◽  
Qian Deng ◽  
Nianyi Sun ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Magnetic Stimulation ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Expression Levels ◽  
Cord Injury ◽  
Group B ◽  
Stimulation Group

Objectives Spinal cord injury (SCI) is a disabling central nervous system disorder. This study aimed to explore the effects of repetitive trans-spinal magnetic stimulation (rTSMS) of different spinal cord segments on movement function and growth-associated protein-43 (GAP43) and 5-hydroxytryptamine (5-HT) expression in rats after acute SCI and to preliminarily discuss the optimal rTSMS treatment site to provide a theoretical foundation and experimental evidence for clinical application of rTSMS in SCI. Methods A rat T10 laminectomy SCI model produced by transient application of an aneurysm clip was used in the study. The rats were divided into group A (sham surgery), group B (acute SCI without stimulation), group C (T6 segment stimulation), group D (T10 segment stimulation), and group E (L2 segment stimulation). Results In vivo magnetic stimulation protected motor function, alleviated myelin sheath damage, decreased NgR and Nogo-A expression levels, increased GAP43 and 5-HT expression levels, and inhibited terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and apoptosis-related protein expression in rats at 8 weeks after the surgery. Conclusions This study suggests that rTSMS can promote GAP43 and 5-HT expression and axonal regeneration in the spinal cord, which is beneficial to motor function recovery after acute SCI.

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