scholarly journals Activation of Three Major Signaling Pathways After Endurance Training and Spinal Cord Injury

2021 ◽  
Author(s):  
Katarina Kiss Bimbova ◽  
Maria Bacova ◽  
Alexandra Kisucka ◽  
Jan Galik ◽  
Peter Zavacky ◽  
...  
Keyword(s):  
Physical Activity ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factors ◽  
Endurance Training ◽  
Signaling Pathways ◽  
Spinal Cord Tissue ◽  
Protein Levels ◽  
Cord Injury ◽  
Survival And Growth

AbstractWe aimed to investigate the effects of endurance training on expression of growth factors (GFs) and stimulation of neurotrophin-dependent signaling pathways (PI3k/Akt, PLCγ/PKC, PLCγ/CAMKII, Ras-Erk1/2 and Rac1-Cdc42) responsible for neuroplasticity, neuroregeneration, survival and growth after spinal cord injury (SCI). Wistar rats were divided into four groups: (i) intact controls; (ii) 6 weeks of endurance training; (iii) SCI; (iv) pre-training + SCI. The animals survived for 6 weeks after SCI. Firstly, endurance training markedly upregulated mRNA expression and protein levels (up to four times) of growth factors (BDNF, GDNF) and their receptors (TrkB, Gfrα) in low thoracic segments (Th8–Th10) compared to levels in untrained animals. Secondly, we found that spontaneous neuroplasticity seen in the SCI alone group was GF-specific and was activated through both PLCγ-PKC and PLC-CAMKII signaling pathways. In addition, training prior to SCI markedly increased the activity of PLCγ-PKC signaling at both transcript and protein levels at and around the lesion site. Similar effects were seen in expression of PI3k/Akt and Ras/Erk1/2 signaling responsible for cell survival and regeneration. Thirdly, rats which underwent physical activity prior to SCI were more active and had significantly better neurological scores at the 14th and 42nd days of survival. These results suggest that regular physical activity could play an important role after SCI, as it maintains increased expression of GFs in spinal cord tissue 6 weeks post-SCI. The BDNF- and/or BDNF + GDNF-dependent signaling pathways were significantly affected in pre-trained SCI animals. In contrast, GDNF-dependent Rac1-Cdc42 signaling was not involved in training-affected SCI response.

Circular Ribonucleic Acid Expression Alteration in the Spinal Cord Tissue after Spinal Cord Injury in Rats

2021 ◽  
pp. 1-20
Author(s):  
Chongxi Xu ◽  
Hui Hu ◽  
Tong Yi ◽  
Xihang Zeng ◽  
Yu Hu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathways ◽  
Spinal Cord Tissue ◽  
Ribonucleic Acids ◽  
Cord Injury ◽  
Whole Transcriptome Sequencing ◽  
Genetic Level ◽  
Mirna Sponges ◽  
The Relationship

<b><i>Background and Purpose:</i></b> Increased researches focus into pathophysiological mechanisms of spinal cord injury (SCI), particularly toward the relationship between relevant biomarkers and the degree of SCI and prognosis. Circular ribonucleic acids (circRNAs) possess microRNA (miRNA) binding sites that can play the role of miRNA sponges and thus participate in the expression of parental gene modification. This study focused on rat SCI models and explore the relationship between circRNAs and SCI at a genomic level. <b><i>Methods:</i></b> We first established a rat SCI model and extracted the target spinal cord tissue according to 4 time points. Then investigated the alterations in the circRNA expression by high-throughput whole transcriptome sequencing, analyzed data by gene ontology and the Kyoto Encyclopedia of Genes and Genomes, and constructed the circRNA-miRNA network. <b><i>Results:</i></b> A total of 178 circRNAs were dysregulated (89 upregulated/89 downregulated). Differential circRNAs were found to be mainly involved in the composition of specific organelles in the cytoplasm and are mainly involved in the energy transfer process associated with electron transfer (and similar activities). In all the signaling pathways identified in this study, the MAPK, Wnt, and mTOR signaling pathways are intimately associated with the pathophysiological process of rats post-SCI. In this study, 10 circRNAs with obvious dysregulation were selected for prediction, 26 miRNAs with additional interactions were obtained, and a network diagram of circRNAs-miRNAs was constructed. In this manner, one can understand in further detail the pathogenesis of SCI and to provide new strategies for the prevention, diagnosis, and treatment of SCI-related injuries at the genetic level.

scholarly journals D-dopachrome tautomerase activates COX2/PGE2 pathway of astrocytes to mediate inflammation following spinal cord injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Huiyuan Ji ◽  
Yuxin Zhang ◽  
Chen Chen ◽  
Hui Li ◽  
Bingqiang He ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signal Pathways ◽  
Post Injury ◽  
Dopachrome Tautomerase ◽  
Protein Levels ◽  
Cytokines And Chemokines ◽  
Cord Injury ◽  
Mitogen Activated Protein ◽  
Spinal Cord Contusion

Abstract Background Astrocytes are the predominant glial cell type in the central nervous system (CNS) that can secrete various cytokines and chemokines mediating neuropathology in response to danger signals. D-dopachrome tautomerase (D-DT), a newly described cytokine and a close homolog of macrophage migration inhibitory factor (MIF) protein, has been revealed to share an overlapping function with MIF in some ways. However, its cellular distribution pattern and mediated astrocyte neuropathological function in the CNS remain unclear. Methods A contusion model of the rat spinal cord was established. The protein levels of D-DT and PGE2 synthesis-related proteinase were assayed by Western blot and immunohistochemistry. Primary astrocytes were stimulated by different concentrations of D-DT in the presence or absence of various inhibitors to examine relevant signal pathways. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results D-DT was inducibly expressed within astrocytes and neurons, rather than in microglia following spinal cord contusion. D-DT was able to activate the COX2/PGE2 signal pathway of astrocytes through CD74 receptor, and the intracellular activation of mitogen-activated protein kinases (MAPKs) was involved in the regulation of D-DT action. The selective inhibitor of D-DT was efficient in attenuating D-DT-induced astrocyte production of PGE2 following spinal cord injury, which contributed to the improvement of locomotor functions. Conclusion Collectively, these data reveal a novel inflammatory activator of astrocytes following spinal cord injury, which might be beneficial for the development of anti-inflammation drug in neuropathological CNS.

scholarly journals The effect of level of injury and physical activity on heart rate variability following spinal cord injury

2017 ◽  
Vol 42 (2) ◽  
pp. 212-219 ◽  
Author(s):  
Athanasios Kyriakides ◽  
Dimitrios Poulikakos ◽  
Angeliki Galata ◽  
Dimitrios Konstantinou ◽  
Elias Panagiotopoulos ◽  
...  
Keyword(s):  
Physical Activity ◽  
Spinal Cord ◽  
Heart Rate ◽  
Spinal Cord Injury ◽  
Heart Rate Variability ◽  
Cord Injury

Spinal Cord Tissue Bridges Validation Study: Predictive Relationships With Sensory Scores Following Cervical Spinal Cord Injury

2021 ◽  
Author(s):  
Andrew C. Smith ◽  
Denise R. O’Dell ◽  
Wesley A. Thornton ◽  
David Dungan ◽  
Eli Robinson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
External Validation ◽  
Inpatient Rehabilitation ◽  
Spinal Cord Tissue ◽  
Light Touch ◽  
Post Injury ◽  
Data Set ◽  
Cord Injury ◽  
Predictive Relationships

Background: Using magnetic resonance imaging (MRI), widths of ventral tissue bridges demonstrated significant predictive relationships with future pinprick sensory scores, and widths of dorsal tissue bridges demonstrated significant predictive relationships with future light touch sensory scores, following spinal cord injury (SCI). These studies involved smaller participant numbers, and external validation of their findings is warranted. Objectives: The purpose of this study was to validate these previous findings using a larger independent data set. Methods: Widths of ventral and dorsal tissue bridges were quantified using MRI in persons post cervical level SCI (average 3.7 weeks post injury), and pinprick and light touch sensory scores were acquired at discharge from inpatient rehabilitation (average 14.3 weeks post injury). Pearson product-moments were calculated and linear regression models were created from these data. Results: Wider ventral tissue bridges were significantly correlated with pinprick scores (r = 0.31, p &lt; 0.001, N = 136) and wider dorsal tissue bridges were significantly correlated with light touch scores (r = 0.31, p &lt; 0.001, N = 136) at discharge from inpatient rehabilitation. Conclusion: This retrospective study’s results provide external validation of previous findings, using a larger sample size. Following SCI, ventral tissue bridges hold significant predictive relationships with future pinprick sensory scores and dorsal tissue bridges hold significant predictive relationships with future light touch sensory scores.

Metabolic syndrome in people with a long-standing spinal cord injury: associations with physical activity and capacity

2016 ◽  
Vol 41 (11) ◽  
pp. 1190-1196 ◽  
Author(s):  
Sonja de Groot ◽  
Jacinthe J. Adriaansen ◽  
Marga Tepper ◽  
Govert J. Snoek ◽  
Lucas H.V. van der Woude ◽  
...  
Keyword(s):  
Physical Activity ◽  
Metabolic Syndrome ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Aerobic Capacity ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
The Metabolic Syndrome ◽  
Cord Injury ◽  
Peak Aerobic Capacity

This study investigated (i) the prevalence of the metabolic syndrome (MetS) in people with a long-standing spinal cord injury (SCI); (ii) whether personal or lesion characteristics are determinants of the MetS; and (iii) the association with physical activity or peak aerobic capacity on the MetS. In a cross-sectional study, persons with SCI (N = 223; time since injury of ≥10 years) were tested. The individual components of the MetS were assessed together with the physical activity measured by the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD), while peak aerobic capacity was tested during a graded wheelchair exercise test on a treadmill. Thirty-nine percent of the participants had MetS. In a multivariate logistic regression analyses and after performing a backward regression analysis, only age and education were significant determinants of the MetS. A 10-year increase in age leads to a 1.5 times more chance to have the MetS. Furthermore, people with a low education will multiply the relative risk of MetS compared with people with high education by almost 2. With and without correcting for confounders, no significant relationship was found between PASIPD or peak aerobic capacity and the MetS. It can be concluded that the prevalence of the MetS is high (39%) in people with a long-standing SCI but is comparable to the general Dutch population. Older people and those with a lower education level are most at risk for the MetS. Physical activity and peak aerobic fitness were not related to the MetS in this group with a long-standing SCI.

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