Therapeutic targets and nanomaterial-based therapies for mitigation of secondary injury after spinal cord injury

Nanomedicine ◽  
2021 ◽  
Vol 16 (22) ◽  
pp. 2013-2028
Author(s):  
Jun Gao ◽  
Minkyung Khang ◽  
Zhen Liao ◽  
Megan Detloff ◽  
Jeoung Soo Lee
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Therapeutic Targets ◽  
Neurological Dysfunction ◽  
Secondary Injury ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier ◽  
And Oxidative Stress

Spinal cord injury (SCI) and the resulting neurological trauma commonly result in complete or incomplete neurological dysfunction and there are few effective treatments for primary SCI. However, the following secondary SCI, including the changes of microvasculature, inflammatory response and oxidative stress around the injury site, may provide promising therapeutic targets. The advances of nanomaterials hold promise for delivering therapeutics to alleviate secondary SCI and promote functional recovery. In this review, we highlight recent achievements of nanomaterial-based therapy, specifically targeting blood–spinal cord barrier disruption, mitigation of the inflammatory response and lightening of oxidative stress after spinal cord injury.

Effect of Electroacupuncture on Spinal Cord Injury in Mice: Inhibition Of Inflammatory Response and Oxidative Stress via ApoE and Nrf2

2020 ◽  
Author(s):  
Ni Dai ◽  
Chenglin Tang ◽  
Hongdi Zhao ◽  
Pan Dai ◽  
Siqin Huang
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Neuroprotective Effect ◽  
Related Factor ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
And Oxidative Stress

Abstract Background: Spinal cord injury (SCI) is a catastrophic central nervous system disease. Inflammatory response and oxidative stress are two critical factors in the pathophysiological process of SCI and closely involved with Apolipoprotein E(ApoE) and Nuclear factor erythroid 2-related factor (Nrf2). Electroacupuncture (EA) has perfectly neuroprotective effect on SCI. However, the underlying mechanism by which EA mediates the inflammatory response and oxidative stress is not completely elucidated. In the present study, we investigated the signaling pathways that EA regulates inflammatory response and oxidative stress through elevation of ApoE and Nrf2 after SCI.Methods: C57BL/6 Wide Type (WT) mice and ApoE -/- mice were subjected to SCI model by a serrefine clamping. Neurological function was detected by BMS scores, ultrastructure of demyelinationed axons was observed by transmission electron microscopy. ApoE, pro- and anti- inflammatory cytokines, oxidative stress-relevant proteins were determined by histochemistry technology. Two-way ANOVA was applied to BMS scores. One-way ANOVA and Bonferroni's multiple comparison test were used to analyse differences among groups.Results: BMS scores were increased gradually and demyelinated axons were improved by EA gradually with the expression of ApoE. EA can inhibit inflammatory response by activation of ApoE, which decreased pro-inflammatory cytokines(TNF-α, IL-6, and IL-1β) expression and increased anti-inflammatory cytokines(IL-10 and TGF-β1).Meanwhile, EA can also inhibit oxidative stress by elevation of Nrf2,which induced HO-1 and NQO1 expression in WT and ApoE -/- mice.Conclusions: EA is a reliable treatment for promoting functional recovery of SCI. Thesynergisticrole of ApoE and Nrf2 in EA regulating inflammatory response and oxidative stress is decisiveto recovery after SCI.

scholarly journals miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Feng Sun ◽  
Haiwei Zhang ◽  
Tianwen Huang ◽  
Jianhui Shi ◽  
Tianli Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Luciferase Reporter ◽  
Spinal Cord Tissue ◽  
Tnf Α ◽  
Cord Injury ◽  
And Oxidative Stress

Objectives. To investigate the roles of miR-221 in spinal cord injury (SCI) as well as the underlying mechanism. Methods. A mouse model of SCI was generated and used to examine dynamic changes in grip strength of the mouse upper and lower limbs. The expression of miR-221 and tumor necrosis factor-α (TNF-α) was detected by RT-qPCR and Western blot. Levels of inflammation and oxidative stress in microglia cells of the injured mice overexpressing miR-221 were then measured by ELISA. Bioinformatics analysis and dual-luciferase reporter assay were conducted to identify the miR-221 target. Results. We successfully constructed SCI mouse model. The results of qRT-PCR showed that miR-221 was gradually upregulated in the spinal cord tissue of mice in the SCI group with the prolonged injury time. At the same time, the mRNA and protein of TNF-α gradually decreased. We further confirmed through cell experiments that the inflammatory factors TNF-α and IL-6, as well as iNOS and eROS, were upregulated in spinal cord microglia cells of SCI mice, and upregulation of miR-122 can inhibit their expression. Finally, the luciferase reporter experiment confirmed that miR-122 targeted TNF-α. Conclusions. We present evidence that miR-221 promotes functional recovery of the injured spinal cord through targeting TNF-α, while alleviating inflammatory response and oxidative stress.

scholarly journals Tauroursodeoxycholic Acid Alleviates Secondary Injury in Spinal Cord Injury Mice Through Reducing Oxidative Stress, Apoptosis, and Inflammatory Response

2021 ◽  
Author(s):  
Yonghui Hou ◽  
Jiyao Luan ◽  
Tiancheng Deng ◽  
Taida Huang ◽  
Xing Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Cortical Neurons ◽  
Axon Regeneration ◽  
Secondary Injury ◽  
Primary Cortical Neurons ◽  
Cord Injury

Abstract Background Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid derivative, which has been demonstrated to have neuroprotective effects in different neurological disease models. However, the effect and underlying mechanism of TUDCA on spinal cord injury (SCI) have not been fully elucidated. This study is aim to investigate the protective effects of TUDCA in SCI mouse model and the related mechanism involved.Methods The primary cortical neurons were isolated from E16.5 C57BL/6 mouse embryos. To evaluate the effect of TUDCA on oxidative stress in vitro, the cortical neurons were treated with H2O2 with or without TUDCA added. Mice were randomly divided into sham, SCI and TUDCA groups. SCI model was induced using a pneumatic impact device at T9-T10 level of vertebra. TUDCA (200 mg/kg) or equal volume of saline was intragastrically administrated daily post injury for 14 days. ResultsWe found that TUDCA reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) release and restored superoxide dismutase (SOD) activity to protect primary cortical neurons from oxidative stress in vitro. In vivo, TUDCA treatment significantly reduced tissue injury, oxidative stress, inflammatory response, and apoptosis; promoted axon regeneration and remyelination in the lesion site of spinal cord of SCI mice. The functional recovery test revealed that TUDCA treatment significantly ameliorated recovery of limb function.ConclusionsTUDCA treatment can alleviate secondary injury and promote functional recovery through reducing oxidative stress, inflammatory response and apoptosis induced by primary injury, and promote axon regeneration and remyelination, which could be used as a potential therapy for human SCI recovery.

scholarly journals CCL3 contributes to secondary damage after spinal cord injury

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Nicolas Pelisch ◽  
Jose Rosas Almanza ◽  
Kyle E. Stehlik ◽  
Brandy V. Aperi ◽  
Antje Kroner
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Lesion Size ◽  
Secondary Injury ◽  
Wild Type ◽  
Locomotor Recovery ◽  
Secondary Damage ◽  
Cord Injury

Abstract Background Secondary damage after spinal cord injury (SCI) is characterized by a cascade of events including hemorrhage, apoptosis, oxidative stress, and inflammation which increase the lesion size which can influence the functional impairment. Thus, identifying specific mechanisms attributed to secondary injury is critical in minimizing tissue damage and improving neurological outcome. In this work, we are investigating the role of CCL3 (macrophage inflammatory protein 1-α, MIP-1α), a chemokine involved in the recruitment of inflammatory cells, which plays an important role in inflammatory conditions of the central and peripheral nervous system. Methods A mouse model of lower thoracic (T11) spinal cord contusion injury was used. We assessed expression levels of CCL3 and its receptors on the mRNA and protein level and analyzed changes in locomotor recovery and the inflammatory response in the injured spinal cord of wild-type and CCL3−/− mice. Results The expression of CCL3 and its receptors was increased after thoracic contusion SCI in mice. We then examined the role of CCL3 after SCI and its direct influence on the inflammatory response, locomotor recovery and lesion size using CCL3−/− mice. CCL3−/− mice showed mild but significant improvement of locomotor recovery, a smaller lesion size and reduced neuronal damage compared to wild-type controls. In addition, neutrophil numbers as well as the pro-inflammatory cytokines and chemokines, known to play a deleterious role after SCI, were markedly reduced in the absence of CCL3. Conclusion We have identified CCL3 as a potential target to modulate the inflammatory response and secondary damage after SCI. Collectively, this study shows that CCL3 contributes to progressive tissue damage and functional impairment during secondary injury after SCI.

scholarly journals Catalpol Protects Against Spinal Cord Injury in Mice Through Regulating MicroRNA-142-Mediated HMGB1/TLR4/NF-κB Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Hougang Xia ◽  
Dandan Wang ◽  
Xiaohui Guo ◽  
Kaidi Wu ◽  
Fuwei Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Factors ◽  
Tunel Staining ◽  
Ros Generation ◽  
Bv2 Cells ◽  
Cord Injury ◽  
Oxidative Response

Background: Spinal cord injury (SCI) is a devastating condition that leads to paralysis, disability and even death in severe cases. Inflammation, apoptosis and oxidative stress in neurons are key pathogenic processes in SCI. Catalpol (CTP), an iridoid glycoside extracted from Rehmannia glutinosa, has many pharmacological activities, such as anti-inflammatory, anti-oxidative and anti-apoptotic properties.Purpose: Here, we investigated whether CTP could exert neuroprotective effects against SCI, and explored the underlying mechanism involved.Methods: SCI was induced by a weight-drop device and treated with CTP (10 mg and 60 mg/kg). Then the locomotor function of SCI mice was evaluated by the BBB scores, spinal cord edema was measured by the wet/dry weight method, oxidative stress markers and inflammatory factors were detected by commercial kits and neuronal death was measured by TUNEL staining. Moreover, the microRNA expression profile in spinal cords from mice following SCI was analyzed using miRNA microarray. In addition, reactive oxygen species (ROS) generation, inflammatory response and cell apoptosis were detected in murine microglia BV2 cells under oxygen-glucose deprivation (OGD) and CTPtreatment.Results: Our data showed that CTP treatment could improve the functional recovery, as well as suppress the apoptosis, alleviate inflammatory and oxidative response in SCI mice. In addition, CTP was found to be up-regulated miR-142 and the protective effects of CTP on apoptosis, inflammatory and oxidative response may relate to its regulation of HMGB1/TLR4/NF-κB pathway through miR-142.Conclusion: Our findings suggest that CTP may protect the spinal cord from SCI by suppression of apoptosis, oxidative stress and inflammatory response via miR-142/HMGB1/TLR4/NF-κB pathway.

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