Effects of FABP7 on functional recovery after spinal cord injury in adult mice

2019 ◽  
Vol 31 (2) ◽  
pp. 291-297 ◽  
Author(s):  
Nobuo Senbokuya ◽  
Hideyuki Yoshioka ◽  
Takashi Yagi ◽  
Yuji Owada ◽  
Hiroyuki Kinouchi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Gene Knockout ◽  
Neuronal Injury ◽  
Wild Type ◽  
Fatty Acid Binding ◽  
Significant Difference ◽  
Cord Injury ◽  
In The Wild

OBJECTIVEElucidating the mechanisms of neuronal injury is crucial for the development of spinal cord injury (SCI) treatments. Brain-type fatty acid–binding protein 7 (FABP7) is expressed in the adult rodent brain, especially in astrocytes, and has been reported to play a role in astrocyte function in various types of brain damage; however, its role after SCI has not been well studied. In this study, the authors evaluated the expression change of FABP7 after SCI using a mouse spinal cord compression model and observed the effect of FABP7 gene knockout on neuronal damage and functional recovery after SCI.METHODSFemale FABP7 knockout (KO) mice with a C57BL/6 background and their respective wild-type littermates were subjected to SCI with a vascular clip. The expression of FABP7, neuronal injury, and functional recovery after SCI were analyzed in both groups of mice.RESULTSWestern blot analysis revealed upregulation of FABP7 in the wild-type mice, which reached its peak 14 days after SCI, with a significant difference in comparison to the control mice. Immunohistochemistry also showed upregulation of FABP7 at the same time points, mainly in proliferative astrocytes. The number of surviving ventral neurons in the FABP7-KO mice at 28 days after SCI was significantly lower than that observed in the wild-type mice. In addition, motor functional recovery in the FABP7-KO mice was significantly worse than that of the wild-type mice.CONCLUSIONSThe findings of this study indicate that FABP7 could have a neuroprotective role that might be associated with modulation of astrocytes after SCI. FABP7 could potentially be a therapeutic target in the treatment of SCI.

The effect of glutamine on locomotor performance and skeletal muscle myosins following spinal cord injury in rats

2006 ◽  
Vol 101 (4) ◽  
pp. 1045-1052 ◽  
Author(s):  
Jamie D. Golding ◽  
Sarah T. Rigley MacDonald ◽  
Bernhard H. J. Juurlink ◽  
Benjamin W. C. Rosser
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Extensor Digitorum Longus ◽  
Critical Role ◽  
Extensor Digitorum ◽  
Secondary Injury ◽  
Significant Difference ◽  
Cord Injury ◽  
Functional Scores

Following initial spinal cord injury (SCI), a cascade of pathological events, including oxidative stress, leads to secondary injury. Glutathione (GSH) plays a critical role in oxidant scavenging. Maintenance of GSH concentrations after SCI lessens secondary injury and improves recovery. Since glutamine promotes GSH synthesis, this nonessential amino acid was examined for therapeutic potential. Denervation alters the expression of myosin heavy chain (MHC) isoforms within skeletal muscles. The hypotheses of this study were that glutamine administration to SCI rats would lead to improved functional recovery and more preserved MHC phenotypes in representative locomotor muscles. Male Wistar rats were divided into four groups: healthy, sham with laminectomy, laminectomized SCI untreated, and laminectomized SCI treated with glutamine. Functional performance was measured weekly for 6 wk using Basso-Beattie-Bresnahan scale and angle board methods. MHC composition of rat soleus and extensor digitorum longus muscles was determined using SDS-PAGE. Glutamine-treated rats had significantly higher angle board scores ( P < 0.001) and Basso-Beattie-Bresnahan scores ( P < 0.01) than untreated SCI rats. Soleus of healthy rats contained 94% type 1 myosin isoform. Treated rats maintained 68%, which was significantly ( P < 0.001) greater than 28% in untreated rats. The extensor digitorum longus of healthy rats contained 55% type 2b myosin. There was a significant ( P < 0.001) decrease in this isoform following SCI, but no significant difference between treated and untreated groups. There were strong correlations between higher functional scores and more preserved MHC phenotypes. Our findings suggest glutamine improves functional recovery and helps preserve myosin profile by reducing secondary SCI, thereby maintaining more nerves.

scholarly journals Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury

2020 ◽  
Vol 11 ◽  
Author(s):  
Roxana Rodríguez-Barrera ◽  
Adrián Flores-Romero ◽  
Vinnitsa Buzoianu-Anguiano ◽  
Elisa Garcia ◽  
Karla Soria-Zavala ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Combination Strategy ◽  
Chronic Spinal Cord Injury ◽  
Cord Injury

scholarly journals Exercise Ameliorates Spinal Cord Injury by Changing DNA Methylation

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 143
Author(s):  
Ganchimeg Davaa ◽  
Jin Young Hong ◽  
Tae Uk Kim ◽  
Seong Jae Lee ◽  
Seo Young Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Treadmill Exercise ◽  
Exercise Group ◽  
Control Group ◽  
Epigenetic Changes ◽  
Cord Injury ◽  
The Brain

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.

scholarly journals Non-invasive approaches to functional recovery after spinal cord injury: Therapeutic targets and multimodal device interventions

2021 ◽  
Vol 339 ◽  
pp. 113612
Author(s):  
Claudio Pizzolato ◽  
Mehmet A. Gunduz ◽  
Dinesh Palipana ◽  
Jingnan Wu ◽  
Gary Grant ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Therapeutic Targets ◽  
Non Invasive ◽  
Cord Injury

Development and Validation of Crosswalks Between FIM® and SCIM III for Voluntary Musculoskeletal Movement Functions

2021 ◽  
pp. 154596832110338
Author(s):  
Linda A. T. Jones ◽  
Chih-Ying Li ◽  
David Weitzenkamp ◽  
John Steeves ◽  
Susie Charlifue ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Systems Of Care ◽  
Functional Independence Measure ◽  
Correlation Coefficients ◽  
Functional Independence ◽  
Cord Injury ◽  
Parametric Analyses ◽  
Development And Validation

Background. In spinal cord injury, there are multiple databases containing information on functional recovery, but data cannot be pooled or compared due to differences in how function is measured. A crosswalk is needed to link or convert scores between instruments. Objectives. To create a crosswalk between the voluntary musculoskeletal movement items in the Functional Independence Measure (FIM®) and the Spinal Cord Independence Measure III (SCIM III) for spinal cord injury. Methods. Retrospective datasets with FIM® and SCIM III on the same people were used to develop (Swiss dataset, n = 662) and validate (US, n = 119, and Canadian datasets, n = 133) the crosswalks. Three different crosswalk methods (expert panel, equipercentile, and Rasch analysis) were employed. We used the correlation between observed scores on FIM® and SCIM III to crosswalked scores as the primary criterion to assess the strength of the crosswalk. Secondary criteria such as score distributions, Cohen’s effect size, point differences, and subgroup invariance were also evaluated. Results. All three methods resulted in strong correlation coefficients, exceeding the primary criterion value of r = .866 (.897–.972). Assessment of secondary criteria suggests the equipercentile and Rasch methods produced the strongest crosswalks. Conclusions. The Rasch FIM®/SCIM III crosswalk is recommended because it is based on co-calibration of linearized measures, allowing for more sophisticated parametric analyses. The crosswalk will allow comparisons of voluntary musculoskeletal functional recovery across international databases using different functional measures, as well as different systems of care and rehabilitation approaches.

scholarly journals CD157 in bone marrow mesenchymal stem cells mediates mitochondrial production and transfer to improve neuronal apoptosis and functional recovery after spinal cord injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Li ◽  
Heyangzi Li ◽  
Simin Cai ◽  
Shi Bai ◽  
Huabo Cai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Neurons ◽  
Functional Recovery ◽  
Mitochondrial Transfer ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells

Abstract Background Recent studies demonstrated that autologous mitochondria derived from bone marrow mesenchymal stem cells (BMSCs) might be valuable in the treatment of spinal cord injury (SCI). However, the mechanisms of mitochondrial transfer from BMSCs to injured neurons are not fully understood. Methods We modified BMSCs by CD157, a cell surface molecule as a potential regulator mitochondria transfer, then transplanted to SCI rats and co-cultured with OGD injured VSC4.1 motor neuron. We detected extracellular mitochondrial particles derived from BMSCs by transmission electron microscope and measured the CD157/cyclic ADP-ribose signaling pathway-related protein expression by immunohistochemistry and Western blotting assay. The CD157 ADPR-cyclase activity and Fluo-4 AM was used to detect the Ca2+ signal. All data were expressed as mean ± SEM. Statistical analysis was analyzed by GraphPad Prism 6 software. Unpaired t-test was used for the analysis of two groups. Multiple comparisons were evaluated by one-way ANOVA or two-way ANOVA. Results CD157 on BMSCs was upregulated when co-cultured with injured VSC4.1 motor neurons. Upregulation of CD157 on BMSCs could raise the transfer extracellular mitochondria particles to VSC4.1 motor neurons, gradually regenerate the axon of VSC4.1 motor neuron and reduce the cell apoptosis. Transplantation of CD157-modified BMSCs at the injured sites could significantly improve the functional recovery, axon regeneration, and neuron apoptosis in SCI rats. The level of Ca2+ in CD157-modified BMSCs dramatically increased when objected to high concentration cADPR, ATP content, and MMP of BMSCs also increased. Conclusion The present results suggested that CD157 can regulate the production and transfer of BMSC-derived extracellular mitochondrial particles, enriching the mechanism of the extracellular mitochondrial transfer in BMSCs transplantation and providing a novel strategy to improve the stem cell treatment on SCI.

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