Nafamostat mesilate attenuates inflammation and apoptosis and promotes locomotor recovery after spinal cord injury

Duan, Huiquan; Wu, Qiuli; Yao, Xuemei; Fan, Baoyou; Shi, Hongbin; Zhao, Chenxi; Zhang, Yan; Лі, Бо; Sun, Chao; Kong, Xiaohong; Zhou, Xin‐Fu; Feng, Shiqing

doi:10.1111/cns.12801

Cited by 33 publications

(35 citation statements)

References 38 publications

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“…BBB score was used to evaluate the recovery of motor function in rats after SCI . Each rat was evaluated and recorded weekly from 1 to 8 weeks after surgery.…”

Section: Methodsmentioning

confidence: 99%

Low frequency pulsed electromagnetic field promotes the recovery of neurological function after spinal cord injury in rats

Yao

Cheng

et al. 2018

Journal Orthopaedic Research

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Low frequency pulsed electromagnetic field (LFPEMF) has been shown to provide anti-inflammatory and antioxidative effects. However, there are no reports on whether LFPEMF can treat spinal cord injury (SCI) and its therapeutic mechanism. Therefore, this study was conducted to investigate whether LFPEMF can promote the recovery of neurological function after SCI in rats and its therapeutic mechanism. Basso-Beattie-Bresnahan (BBB) score and transcranial magnetic motor-evoked potentials (tcMMEPs) were recorded to assess the recovery of neurological function. Hematoxylin and eosin (HE) staining and luxol fast blue (LFB) staining were performed to assess the severity of SCI. Immunofluorescence (IF) staining and western blotting (WB) were performed to assess the differentiation of oligodendrocyte precursor cells (OPCs) into oligodendrocytes (OLs). Toluidine blue (TB) staining was performed to assess remyelination. WB and enzyme-linked immunosorbent assays (ELISA) were performed to assess the expression of neurotrophins and inflammatory factors. Our results showed that following stimulation by LFPEMF, there were significant improvements in BBB scores, tcMMEP amplitudes, the extent of the damage, and reduced demyelination in rats after SCI. The mature OLs, the number of well-myelinated fibers, and the myelin sheath thickness significantly increased in rats stimulated by LFPEMF after SCI. The expression of neurotrophins significantly increased, and the expression of inflammatory factors significantly decreased in rats stimulated by LFPEMF after SCI. Therefore, we suggest that LFPEMF can promote the recovery of neurological function in rats after SCI by improving the differentiation of OPCs into OLs and promoting remyelination, as well as by inhibiting inflammation and promoting neurotrophic effects. ß

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“…BBB score was used to evaluate the recovery of motor function in rats after SCI . Each rat was evaluated and recorded weekly from 1 to 8 weeks after surgery.…”

Section: Methodsmentioning

confidence: 99%

Low frequency pulsed electromagnetic field promotes the recovery of neurological function after spinal cord injury in rats

Yao

Cheng

et al. 2018

Journal Orthopaedic Research

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“…Together, primary and secondary injuries lead to irreversible neuronal damage, which ultimately culminates in poor functional recovery of patients following SCI [9]. Thus, preventing irreversible damage by targeting pathways of programmed cell death such as apoptosis, pyroptosis, and autophagy may be a promising strategy for treating SCI [10][11][12].…”

Section: Ivyspringmentioning

confidence: 99%

Betulinic acid inhibits pyroptosis in spinal cord injury by augmenting autophagy via the AMPK-mTOR-TFEB signaling pathway

Wu¹,

Chen²,

Zhuang³

et al. 2021

Int. J. Biol. Sci.

101

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Spinal cord injury (SCI) results in a wide range of disabilities. Its complex pathophysiological process limits the effectiveness of many clinical treatments. Betulinic acid (BA) has been shown to be an effective treatment for some neurological diseases, but it has not been studied in SCI. In this study, we assessed the role of BA in SCI and investigated its underlying mechanism. We used a mouse model of SCI, and functional outcomes following injury were assessed. Western blotting, ELISA, and immunofluorescence techniques were employed to analyze levels of autophagy, mitophagy, pyroptosis, and AMPK-related signaling pathways were also examined. Our results showed that BA significantly improved functional recovery following SCI. Furthermore, autophagy, mitophagy, ROS level and pyroptosis were implicated in the mechanism of BA in the treatment of SCI. Specifically, our results suggest that BA restored autophagy flux following injury, which induced mitophagy to eliminate the accumulation of ROS and inhibits pyroptosis. Further mechanistic studies revealed that BA likely regulates autophagy and mitophagy via the AMPK-mTOR-TFEB signaling pathway. Those results showed that BA can significantly promote the recovery following SCI and that it may be a promising therapy for SCI.

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“…Sildenafil citrate, a phosphodiesterase inhibitor, was found to exert a neuroprotective effect on the spinal cord after ischemia/reperfusion injury by attenuating inflammatory mediators [ 19 ]. Our team’s previous study showed that a synthetic serine protease inhibitor, nafamostat mesylate, could attenuate inflammation and apoptosis and promote locomotor recovery after SCI [ 20 ]. Other biological events play an early protective role, such as the defense response caused by the response to stress.…”

Section: Discussionmentioning

confidence: 99%

Isobaric Tagging for Relative and Absolute Protein Quantification (iTRAQ)-Based Quantitative Proteomics Analysis of Differentially Expressed Proteins 1 Week After Spinal Cord Injury in a Rat Model

et al. 2020

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Background Spinal cord injury (SCI) is a devastating trauma of the central nervous system (CNS), with high levels of morbidity, disability, and mortality. One week after SCI may be a critical time for treatment. Changes in protein expression have crucial functions in nervous system diseases, although the effects of changes occurring 1 week after SCI on patient outcomes are unclear. Material/Methods Protein expression was examined in a rat contusive SCI model 1 week after SCI. Differentially expressed proteins (DEPs) were identified by isobaric tagging for relative and absolute protein quantification (iTRAQ)-coupled liquid chromatography tandem-mass spectrometry (LC-MS/MS) proteomics analysis. Gene Ontology (GO) analysis was performed to identify the biological processes, molecular functions, and cellular component terms of the identified DEPs, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to identify key enriched pathways. Protein–protein interaction (PPI) networks were analyzed to identify the top 10 high-degree core proteins. Results Of the 295 DEPs identified, 204 (69.15%) were upregulated and 91 (30.85%) were downregulated 1 week after injury. The main cellular components, molecular functions, biological processes, and pathways identified may be crucial mechanisms involved in SCI. The top 10 high-degree core proteins were complement component C3 (C3), alpha-2-HS-glycoprotein (Ahsg), T-kininogen 1 (Kng1), Serpinc1 protein (Serpinc1), apolipoprotein A-I (Apoa1), serum albumin (Alb), disulfide-isomerase protein (P4hb), transport protein Sec61 subunit alpha isoform 1 (Sec61a1), serotransferrin (Tf), and 60S ribosomal protein L15 (Rpl15). Conclusions The proteins identified in this study may provide potential targets for diagnosis and treatment 1 week after SCI.

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Nafamostat mesilate attenuates inflammation and apoptosis and promotes locomotor recovery after spinal cord injury

Abstract: Upon NM treatment, the functional and histological outcomes were improved, and microenvironment upon SCI was modulated. As a clinically approved drug, NM holds promise for clinical use after spinal cord injury.

Cited by 33 publications

References 38 publications

Low frequency pulsed electromagnetic field promotes the recovery of neurological function after spinal cord injury in rats

Low frequency pulsed electromagnetic field promotes the recovery of neurological function after spinal cord injury in rats

Betulinic acid inhibits pyroptosis in spinal cord injury by augmenting autophagy via the AMPK-mTOR-TFEB signaling pathway

Isobaric Tagging for Relative and Absolute Protein Quantification (iTRAQ)-Based Quantitative Proteomics Analysis of Differentially Expressed Proteins 1 Week After Spinal Cord Injury in a Rat Model

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