Therapeutic effect of metformin on inflammation and apoptosis after spinal cord injury in rats through the Wnt/β-catenin signaling pathway

Zhang, Tao; Wang, Fang; Li, Kang; Lv, Chengwei; Gao, Kai; Lv, Chaoliang

doi:10.1016/j.neulet.2020.135440

Cited by 28 publications

(33 citation statements)

References 31 publications

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“…In addition, apoptosis acts an important role during neurons death and spinal cord microcirculatory damage after SCI [ 34 ]. It was reported that metformin could reduce inflammation and apoptosis, and promote functional recovery of SCI rats through activating Wnt/β-catenin [ 11 ]. Wnt-3a could improve functional recovery through autophagy activation via inhibiting the mTOR signaling pathway after SCI [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the group SCI+resveratrol, 30 mg/kg of resveratrol was injected intraperitoneally daily for the first 14 days after SCI. In the group SCI+resveratrol+XAV939, 0.5 mg/kg of XAV939 and 30 mg/kg of resveratrol were injected intraperitoneally daily for the first 14 days after SCI [ 11 , 16 ]. Same amount of saline was injected in the group sham and SCI.…”

Section: Methodsmentioning

confidence: 99%

“…Wnts containing wnt1, wnt3, and wnt5, are known as glycoproteins. Wnts have been proved to be closely related with cell proliferation, invasion, migration, and apoptosis in several pathological processes including tumor, myocardial ischemia reperfusion injury, and SCI [ 11 – 13 ]. Previous studies also confirmed the regulatory role of Wnt/β-catenin signaling pathway in the SCI process.…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol promotes axonal regeneration after spinal cord injury through activating Wnt/β-catenin signaling pathway

Xiang

Zhang

Yao

et al. 2021

Aging

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Background: Spinal cord injury (SCI) is characterized by autonomic dysreflexia, chronic pain, sensory and motor deficits. Resveratrol has shown potential neuroprotective function in several neurodegenerative diseases’ models. However, if resveratrol could improve the function recovery after SCI and the further mechanism have not been investigated. Methods: SCI rat model was established through laminectomy at lamina T9-10 aseptically. Basso, beattie and bresnahan (BBB) and inclined plane score, sensory recovery, spinal cord content, and inflammatory factors were measured. The levels of GAP43, NF421, GFAP, Bax, Bcl-2 and caspase-3 were measured using immunohistochemical staining. Tunel staining was applied to detect apoptosis level. Results: Resveratrol significantly improved the function recovery, promoted axonal regeneration, suppressed apoptosis after SCI. The activation of Wnt/β-catenin signaling pathway was achieved by resveratrol. XAV939 significantly reversed the influence of resveratrol on function recovery, axonal regeneration, apoptosis after SCI. Conclusions: Resveratrol could promote the function recovery and axonal regeneration, improve histological damage, inhibit apoptosis level after SCI through regulating Wnt/β-catenin signaling pathway. This research expanded the regulatory mechanism of resveratrol in SCI injury.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Resveratrol promotes axonal regeneration after spinal cord injury through activating Wnt/β-catenin signaling pathway

Xiang

Zhang

Yao

et al. 2021

Aging

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“…Characteristics of the studies included in this meta-analysis are presented in Table 1 . Six studies are from China [ 14 – 16 , 20 – 23 ] and 1 from Iran [ 24 ]. Five studies used female Sprague-Dawley rats [ 14 – 16 , 20 – 22 ], and 2 studies used male Sprague-Dawley rats [ 23 , 24 ].…”

Section: Resultsmentioning

confidence: 99%

“…Six studies are from China [ 14 – 16 , 20 – 23 ] and 1 from Iran [ 24 ]. Five studies used female Sprague-Dawley rats [ 14 – 16 , 20 – 22 ], and 2 studies used male Sprague-Dawley rats [ 23 , 24 ]. All rats weighed 180-260 g. Three studies used a rat model of spinal cord compression [ 16 , 21 , 22 ].…”

Section: Resultsmentioning

confidence: 99%

Effect of Metformin on Locomotor Function Recovery in Rat Spinal Cord Injury Model: A Meta-analysis

Chen

Dong-yang

Qiuju

et al. 2021

Oxidative Medicine and Cellular Longevity

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Background. Disorder of locomotor function is universal in patients with spinal cord injury (SCI) and has a severe impairment on their quality of life. Metformin, the first-line antidiabetic drug, has been used to improve locomotor function in SCI rats through antioxidative mechanisms recently. Methods. A search strategy was conducted from databases, including PubMed, Web of Science, MEDLINE, and Scopus database until April 2021. The methodological quality of the animal experimental studies was assessed according to the Systematic Review Centre for Laboratory animal Experimentation’s Risk of Bias tool. The weighted mean difference was calculated with the random-effects model. Results. Seven eligible studies on SCI and metformin were reviewed. The meta-analysis indicated that SCI rats receiving metformin therapy showed a significant locomotor function recovery. Limitations and no obvious publication bias were presented in the studies. Conclusion. Metformin can promote the recovery of the locomotor function of SCI rats. However, the use of this meta-analysis was influenced due to the not high quality of studies. Consequently, more high-quality studies are necessary for preclinical studies of SCI in the future.

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Comprehensive analysis of m6A methylation modification in chronic spinal cord injury in mice

Liu

Zhao

Qin

et al. 2022

Journal Orthopaedic Research

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Chronic spinal cord injury (CSCI) is a catastrophic disease of the central nervous system (CNS), resulting in partial or complete loss of neurological function. N6-methyladenosine (m6A) is the most common form of reversible posttranslational modi cation at the RNA level. However, the role of m6A modi cation in CSCI remains unknown. In this study, we established a CSCI model using a water-absorbable polyurethane polymer, with behavioral assessment, electrophysiological analysis, and histochemical staining for validation. Methylated RNA immunoprecipitation sequencing (meRIP-seq) and mRNA sequencing (mRNA-seq) were jointly explored to compare the differences in CSCI spinal tissue and normal spinal tissue. Furthermore, qRT-PCR, western blotting, and immuno uorescence staining were used to analyze m6A modi cation-related proteins. We found that water-absorbable polyurethane polymer well simulated chronic spinal cord compression. BMS scores and electrophysiological analysis showed continuous neurological function decline after chronic compression of the spinal cord. meRIP-seq identi ed 642 differentially modi ed m6A genes, among which 263 genes were downregulated and 379 genes were upregulated. mRNA-seq showed that 1544 genes were upregulated and 290 genes were downregulated after CSCI. Gene Ontology (GO) terms and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were also identi ed. qRT-PCR, western blotting, and immuno uorescence staining showed that Mettl14 was signi cantly upregulated after CSCI. Our study revealed a comprehensive pro le of m6A modi cations in CSCI and may provide a valuable tool for further research on CSCI. study showed that mettl14 was signi cantly overexpressed after CSCI and mainly expressed in neurons, which was further validated by qRT-PCR, western blotting, and immuno uorescence.Our study is not without limitations. First, we obtained whole spinal tissue for meRIP-seq and mRNA-seq. Although the total m6A modi cations were assessed, it was di cult to distinguish m6A methylation changes in speci c cell types. In further in-depth research, extracting speci c cells for veri cation of m6A modi cation and exploring its function would be meaningful. Second, we performed preliminary analyses of differentially expressed genes and enriched GO and KEGG pathways, but their roles in CSCI require further validation through extensive experiments.Collectively, our study analyzed m6A methylation modi cations in spinal cord tissue after CSCI. The results indicated that m6A plays an important role in the process of CSCI. Our research may provide new insights for further study of the CSCI pathological process and potential treatment options. DeclarationsAuthor contributions JH, YC and HL designed the study. CL and JZ carried out most of the experiments and data analysis. YJ, TQ, CD and TW assisted in experiments and data analysis. CL drafted the manuscript, and JH and YC revised the manuscript.

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Therapeutic effect of metformin on inflammation and apoptosis after spinal cord injury in rats through the Wnt/β-catenin signaling pathway

Cited by 28 publications

References 31 publications

Resveratrol promotes axonal regeneration after spinal cord injury through activating Wnt/β-catenin signaling pathway

Resveratrol promotes axonal regeneration after spinal cord injury through activating Wnt/β-catenin signaling pathway

Effect of Metformin on Locomotor Function Recovery in Rat Spinal Cord Injury Model: A Meta-analysis

Comprehensive analysis of m6A methylation modification in chronic spinal cord injury in mice

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