scholarly journals Sodium Tanshinone IIA Sulfonate Promotes Spinal Cord Injury Repair  by Inhibiting BSCB Disruption In Vitro and In Vivo

2020 ◽  
Author(s):  
Dan Luo ◽  
Xing Li ◽  
Jiheng Zhan ◽  
Yonghui Hou ◽  
Jiyao Luan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tanshinone Iia ◽  
Neurological Deficits ◽  
Drug Candidate ◽  
Therapeutic Effects ◽  
Spinal Cord Tissue ◽  
Cord Injury ◽  
Sodium Tanshinone Iia Sulfonate

Abstract Background:Spinal cord injury (SCI) leads to microvascular damage and the destruction of blood spinal cord barrier (BSCB), which progresses to secondary injuries like apoptosis and necrosis of neurons and glia, culminating in permanent neurological deficits. BSCB restoration is the primary goal of SCI therapy, although very few drugs can repair the damaged barrier structure and permeability. Sodium tanshinone IIA sulfonate (STS) is commonly used to treat cardiovascular disease. We found that STS restored BSCB integrity and promoted microvessel recovery 7 days after SCI in a mouse model. However, the therapeutic effects of STS on damaged BSCB in the early stage of SCI remained uncertain. Methods: we exposed spinal cord microvascular endothelial cells (SCMECs) to H2O2 and treated them with different doses of STS. The mice received intraperitoneal injection of STS after SCI in vivo model. Spinal cord tissue was taken 1 and 3d post-SCI. HE, Nissl staining, BSCB permeability, and the expression levels of tight junction (TJ) and adherens junction (AJ), MMP2, MMP9, NeuN, and C-caspase-3 were analyzed.Results: In addition to protecting the cells from H2O2-induced apoptosis, STS also reduced cellular permeability. In the in vivo model of SCI as well, STS reduced BSCB permeability, relieved tissue edema and hemorrhage, suppressed MMPs activation and prevented TJ and AJ the loss of proteins. Conclusions:Our findings indicate that STS treatment promotes SCI recovery, and should be investigated further as a drug candidate against traumatic SCI.

scholarly journals In Vivo Tissue-Level Thresholds for Spinal Cord Injury

2007 ◽  
Author(s):  
Jason Maikos ◽  
Ragi Elias ◽  
Zhen Qian ◽  
Dimitris Metaxas ◽  
David Shreiber
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Small Animal ◽  
Tissue Level ◽  
Spine Injury ◽  
Spinal Cord Tissue ◽  
Element Analysis ◽  
In Vivo Models ◽  
Cord Injury

Traumatic loading conditions, such as those experienced during car accidents or falls, can lead to spinal cord injury (SCI), resulting in permanent functional damage [1]. A better understanding of the biomechanical causes of SCI and knowledge of the tolerance of spinal cord tissue to mechanical loading is critical in understanding how mechanisms of injury lead to neurologic deficits, as well as designing methods to prevent SCI. Finite element analysis (FEA) has become an important and cost effective tool to investigate the biomechanics of trauma. FEA has been used to study a variety of biomechanical analyses of trauma, including brain injury and spine injury biomechanics, but there have been limited analyses on spinal cord injury (SCI) [2–5]. In fact, despite the prevalence of small animal models in the neuroscience community used to study SCI, there have been no published analyses of in vivo models of SCI.

scholarly journals Effects of Magnetically Guided, SPIO-Labeled, and Neurotrophin-3 Gene-Modified Bone Mesenchymal Stem Cells in a Rat Model of Spinal Cord Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Rui-Ping Zhang ◽  
Ling-Jie Wang ◽  
Sheng He ◽  
Jun Xie ◽  
Jian-Ding Li
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Therapeutic Effects ◽  
Magnetic Targeting ◽  
Bone Mesenchymal Stem Cells ◽  
Cord Injury

Despite advances in our understanding of spinal cord injury (SCI) mechanisms, there are still no effective treatment approaches to restore functionality. Although many studies have demonstrated that transplantingNT3gene-transfected bone marrow-derived mesenchymal stem cells (BMSCs) is an effective approach to treat SCI, the approach is often low efficient in the delivery of engrafted BMSCs to the site of injury. In this study, we investigated the therapeutic effects of magnetic targeting ofNT3gene-transfected BMSCs via lumbar puncture in a rat model of SCI. With the aid of a magnetic targeting cells delivery system, we can not only deliver the engrafted BMSCs to the site of injury more efficiently, but also perform cells imaging in vivo using MR. In addition, we also found that this composite strategy could significantly improve functional recovery and nerve regeneration compared to transplantingNT3gene-transfected BMSCs without magnetic targeting system. Our results suggest that this composite strategy could be promising for clinical applications.

scholarly journals Therapy of spinal cord injury by zinc modified gold nanoclusters via immune-suppressing strategies

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sen Lin ◽  
Dan Li ◽  
Zipeng Zhou ◽  
Chang Xu ◽  
Xifan Mei ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Gold Nanoclusters ◽  
Racemic Mixture ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Effects ◽  
Cord Injury ◽  
Clinical Survey

Abstract Background Spinal cord injury (SCI) is damage to the central nervous system (CNS) that causes devastating complications from chronic pain to breathing problems. Unfortunately, few effective and safe treatments are known to relieve the damages of SCI. Nanomedicines are used for the treatment of SCI with relatively few side effects, but only depending on the delivery of additional drugs, which increase complexity to the treatment. Considering the urgent need for saving SCI patients, it is important to develop promising nanobiotechnology for relieving their pains. Methods The clinical survey was used to investigate SCI patients, thereafter the therapy plan was designed. The receiver-operating characteristics (ROC) curves of the prediction model were built to find symptoms after SCI. The treatment plan (i.e. immunosuppressive strategy) was designed by manufacturing therapies based on gold nanoclusters (AuNCs). The response of the immune cells (macrophages) was studied accordingly. The western blot, reactive oxygen species (ROS) activity assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (RT-qPCR), and immunochemical staining were used for evaluation of the in vivo and in vitro therapeutic effects. Results We found increased monocytes/macrophages (M/Ms) levels in 114 SCI subjects (44.7% with severe SCI complications) by the clinical survey. Additionally, the enhanced macrophage level was found to be closely related to the walking disorder after SCI. Since macrophages were central effector cells of the immune system, we assumed that the immune-suppressing strategies could be used for SCI therapy. Thereafter, AuNCs were stabilized by dihydrolipoic acid (DHLA) enantiomers (including DL-DHLA, R-DHLA; A racemic mixture (R and S) was denoted as DL; R and S refer to Rectus and Sinister), obtaining DL-DHLA-AuNCs and R-DHLA-AuNCs, respectively. In addition, zinc-modified DL-DHLA and R-DHLA stabilized AuNCs (i.e., DL-DHLA-AuNCs-Zn and R-DHLA-AuNCs-Zn) were investigated. Among these AuNCs, R-DHLA-AuNCs-Zn showed the most remarkable therapeutic effect for promoting the polarization of pro-inflammatory macrophages and reducing neuronal ROS-induced apoptosis and inflammation in vitro and in vivo; the lesion size was decreased and the survival rate of ventral neurons is higher. Conclusions R-DHLA-AuNCs-Zn have comprehensive therapeutic capabilities, especially the immune-suppressing effects for the therapy of SCI, which is promising to relieve the pain or even recover SCI for the patients. Graphical abstract

scholarly journals Pericytes Make Spinal Cord Breathless after Injury

2017 ◽  
Vol 24 (5) ◽  
pp. 440-447 ◽  
Author(s):  
Viviani M. Almeida ◽  
Ana E. Paiva ◽  
Isadora F. G. Sena ◽  
Akiva Mintz ◽  
Luiz Alexandre V. Magno ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Therapeutic Interventions ◽  
Neurological Deficits ◽  
Detailed Knowledge ◽  
Secondary Damage ◽  
Cord Injury ◽  
Specific Proteins

Traumatic spinal cord injury is a devastating condition that leads to significant neurological deficits and reduced quality of life. Therapeutic interventions after spinal cord lesions are designed to address multiple aspects of the secondary damage. However, the lack of detailed knowledge about the cellular and molecular changes that occur after spinal cord injury restricts the design of effective treatments. Li and colleagues using a rat model of spinal cord injury and in vivo microscopy reveal that pericytes play a key role in the regulation of capillary tone and blood flow in the spinal cord below the site of the lesion. Strikingly, inhibition of specific proteins expressed by pericytes after spinal cord injury diminished hypoxia and improved motor function and locomotion of the injured rats. This work highlights a novel central cellular population that might be pharmacologically targeted in patients with spinal cord trauma. The emerging knowledge from this research may provide new approaches for the treatment of spinal cord injury.

Effect of delayed local cooling on experimental spinal cord injury

1975 ◽  
Vol 42 (2) ◽  
pp. 150-154 ◽  
Author(s):  
Phudhiphorn Thienprasit ◽  
Heinrich Bantli ◽  
James R. Bloedel ◽  
Shelley N. Chou
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neurological Deficits ◽  
Therapeutic Effects ◽  
Evoked Responses ◽  
Local Cooling ◽  
Content Type ◽  
Experimental Spinal Cord Injury ◽  
Cord Injury ◽  
Fine Print

✓ The authors report studies indicating that delayed local cooling is effective in minimizing the neurological deficits of experimental spinal cord injury in cats. Cortical evoked responses were useful in predicting the neurological outcome; untreated animals whose evoked response disappeared for 6 hours failed to recover whereas all treated animals in the same group recovered dramatically. Decompression by laminectomy alone proved ineffective. Possible explanations for the therapeutic effects of cooling and the significance of the delay are briefly discussed.

scholarly journals Comprehensive Effects of Suppression of MicroRNA-383 in Human Bone-Marrow-Derived Mesenchymal Stem Cells on Treating Spinal Cord Injury

2018 ◽  
Vol 47 (1) ◽  
pp. 129-139 ◽  
Author(s):  
Guo-Jun Wei ◽  
Ke-wen Zheng ◽  
Gang An ◽  
Zuo-Wei Shi ◽  
Kai-Fu Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Luciferase Reporter ◽  
Therapeutic Effects ◽  
Cord Injury

Background/Aims: Transplantation of bone-marrow-derived mesenchymal stem cells (MSCs) promotes neural cell regeneration after spinal cord injury (SCI). Recently, we showed that suppression of microRNA-383 (miR-383) in MSCs increased the protein levels of glial cell line derived neurotrophic factor (GDNF), resulting in improved therapeutic effects on SCI. However, the overall effects of miR-383 suppression in MSCs on SCI therapy were not determined yet. Here, we addressed this question. Methods: We used bioinformatics tools to predict all miR-383-targeting genes, confirmed the functional bindings in a dual luciferase reporter assay. The effects of alteration of candidate genes in MSCs on cell proliferation were analyzed by MTT assay and by Western blotting for PCNA. The effects on angiogenesis were assessed by HUVEC assay. The effects on SCI in vivo were analyzed by transplantation of the modified MSCs into nude rats that underwent SCI. Results: Suppression of miR-383 in MSCs not only upregulated GDNF protein, but also increased vascular endothelial growth factor A (VEGF-A) and cyclin-dependent kinase 19 (CDK19), two other miR-383 targets. MiR-383-suppression-induced increases in CDK19 resulted in a slight but significant increase in MSC proliferation, while miR-383-suppression-induced increases in VEGF-A resulted in a slight but significant increase in MSC-mediated angiogenesis. Conclusions: Upregulation of CDK19 and VEGF-A by miR-383 suppression in MSCs further improve the therapeutic potential of MSCs in treating SCI in rats.

Therapeutic Effects of Azithromycin on Spinal Cord Injury in Male Wistar Rats: A Role for Inflammatory Pathways

2021 ◽  
Author(s):  
Ali Rismanbaf ◽  
Khashayar Afshari ◽  
Mehdi Ghasemi ◽  
Abolfazl Badripour ◽  
Arvin Haj-Mirzaian ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Wistar Rats ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Therapeutic Effects ◽  
Spinal Cord Tissue ◽  
Cord Injury ◽  
Male Wistar Rats

Abstract Background Inflammatory responses, including macrophages/microglia imbalance, are associated with spinal cord injury (SCI) complications. Accumulating evidence also suggests an anti-inflammatory property of azithromycin (AZM). Material and Methods Male Wistar rats were subjected to T9 vertebra laminectomy. SCI was induced by spinal cord compression at this level with an aneurysmal clip for 60 seconds. They were divided into three groups: the sham-operated group and two SCI treatment (normal saline as a vehicle control vs. AZM at 180 mg/kg/d intraperitoneally for 3 days postsurgery; first dose: 30 minutes after surgery) groups. Locomotor scaling and behavioral tests for neuropathic pain were evaluated and compared through a 28-day period. At the end of the study, tissue samples were taken to assess neuroinflammatory changes and neural demyelination using ELISA and histopathologic examinations, respectively. In addition, the proportion of M1/M2 macrophage polarization was assessed by using flow cytometry. Results Post-SCI AZM treatment (180 mg/kg/d for 3 days) significantly improved locomotion (p < 0.01) and decreased sensitivity to mechanical (p < 0.01) and thermal allodynia (p < 0.001). Moreover, there was a significant tumor necrosis factor-α (TNF-α) decline (p < 0.01) and interleukin-10 (IL-10) elevation (p < 0.01) in the spinal cord tissue of the AZM-treated group compared with the control groups 28 days post-SCI. AZM significantly improved neuroinflammation as evidenced by reduction of the M1 expression, elevation of M2 macrophages, and reduction of the M1/M2 ratio in both the dorsal root ganglion and the spinal cord tissue after SCI compared with controls (p < 0.01). Conclusion AZM treatment can be considered a therapeutic agent for SCI, as it could reduce neuroinflammation and SCI sensory/locomotor complications.

scholarly journals MicroRNA-182 improves spinal cord injury in mice by modulating apoptosis and the inflammatory response via IKKβ/NF-κB

2021 ◽  
Author(s):  
Min Fei ◽  
Zheng Li ◽  
Yuanwu Cao ◽  
Chang Jiang ◽  
Haodong Lin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Cell Damage ◽  
Secondary Injury ◽  
Spinal Cord Tissue ◽  
Iκb Kinase ◽  
Cord Injury

AbstractSpinal cord injury (SCI) is one common neurological condition which involves primary injury and secondary injury. Neuron inflammation and apoptosis after SCI is the most important pathological process of this disease. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. First, by re-analysis of Gene Expression Omnibus dataset (accession GSE19890), miR-182 was selected for further study because of its suppressive effects on the inflammatory response in the various types of injuries. Functional experiments demonstrated that miR-182 overexpression promoted functional recovery, reduced histopathological changes, and alleviated spinal cord edema in mice. It was also observed that miR-182 overexpression reduced apoptosis and attenuated the inflammatory response in spinal cord tissue, as evidenced by the reduction of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, and the induction of IL-10. Using a lipopolysaccharide (LPS)-induced SCI model in BV-2 cells, we found that miR-182 was downregulated in the BV-2 cells following LPS stimulation, and upregulation of miR-182 improved LPS-induced cell damage, as reflected by the inhibition of apoptosis and the inflammatory response. IκB kinase β (IKKβ), an upstream target of the NF-κB pathway, was directly targeted by miR-182 and miR-182 suppressed its translation. Further experiments revealed that overexpression of IKKβ reversed the anti-apoptosis and anti-inflammatory effects of miR-182 in LPS stimulated BV-2 cells. Finally, we found that miR-182 overexpression blocked the activation of the NF-κB signaling pathway in vitro and in vivo, as demonstrated by the downregulation of phosphorylated (p‑) IκB-α and nuclear p-p65. Taken together, these data indicate that miR-182 improved SCI-induced secondary injury through inhibiting apoptosis and the inflammatory response by blocking the IKKβ/NF-κB pathway. Our findings suggest that upregulation of miR-182 may be a novel therapeutic target for SCI.

scholarly journals MicroRNA-145-Mediated KDM6A Downregulation Enhances Neural Repair after Spinal Cord Injury via the NOTCH2/Abcb1a Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Changzhao Gao ◽  
Fei Yin ◽  
Ran Li ◽  
Qing Ruan ◽  
Chunyang Meng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Pc12 Cells ◽  
Functional Recovery ◽  
Pc12 Cell ◽  
Spinal Cord Tissue ◽  
Neural Repair ◽  
Cord Injury

Spinal cord injury (SCI) causes a significant physical, emotional, social, and economic burden to millions of people. MicroRNAs are known players in the regulatory circuitry of the neural repair in SCI. However, most microRNAs remain uncharacterized. Here, we demonstrate the neuroprotection of microRNA-145 (miR-145) after SCI in vivo and in vitro. In silico analysis predicted the target gene KDM6A of miR-145. The rat SCI model was developed by weight drop, and lipopolysaccharide- (LPS-) induced PC12 cell inflammatory injury model was also established. We manipulated the expression of miR-145 and/or KDM6A both in vivo and in vitro to explain their roles in rat neurological functional recovery as well as PC12 cell activities and inflammation. Furthermore, we delineated the mechanistic involvement of NOTCH2 and Abcb1a in the neuroprotection of miR-145. According to the results, miR-145 was poorly expressed and KDM6A was highly expressed in the spinal cord tissue of the SCI rat model and LPS-induced PC12 cells. Overexpression of miR-145 protects PC12 cells from LPS-induced cell damage and expedites neurological functional recovery of SCI in rats. miR-145 was validated to target and downregulate the demethylase KDM6A expression, thus abrogating the expression of Abcb1a by promoting the methylation of NOTCH2. Additionally, in vivo findings verified that miR-145 expedites neuroprotection after SCI by regulating the KDM6A/NOTCH2/Abcb1a axis. Taken together, miR-145 confers neuroprotective effects and enhances neural repair after SCI through the KDM6A-mediated NOTCH2/Abcb1a axis.

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