scholarly journals Diosgenin Glucoside Protects against Spinal Cord Injury by Regulating Autophagy and Alleviating Apoptosis

2018 ◽  
Vol 19 (8) ◽  
pp. 2274 ◽  
Author(s):  
Xian-Bing Chen ◽  
Zi-Li Wang ◽  
Qing-Yu Yang ◽  
Fang-Yu Zhao ◽  
Xiao-Li Qin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Treated Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Traumatic Lesion ◽  
Cord Injury

Spinal cord injury (SCI) is a severe traumatic lesion of central nervous system (CNS) with only a limited number of restorative therapeutic options. Diosgenin glucoside (DG), a major bioactive ingredient of Trillium tschonoskii Max., possesses neuroprotective effects through its antioxidant and anti-apoptotic functions. In this study, we investigated the therapeutic benefit and underlying mechanisms of DG treatment in SCI. We found that in Sprague-Dawley rats with traumatic SCI, the expressions of autophagy marker Light Chain 3 (LC3) and Beclin1 were decreased with concomitant accumulation of autophagy substrate protein p62 and ubiquitinated proteins, indicating an impaired autophagic activity. DG treatment, however, significantly attenuated p62 expression and upregulated the Rheb/mTOR signaling pathway (evidenced as Ras homolog enriched in brain) due to the downregulation of miR-155-3p. We also observed significantly less tissue injury and edema in the DG-treated group, leading to appreciable functional recovery compared to that of the control group. Overall, the observed neuroprotection afforded by DG treatment warrants further investigation on its therapeutic potential in SCI.

Neuroprotective effects of granulocyte colony-stimulating factor and relationship to promotion of angiogenesis after spinal cord injury in rats

2011 ◽  
Vol 15 (4) ◽  
pp. 414-421 ◽  
Author(s):  
Junko Kawabe ◽  
Masao Koda ◽  
Masayuki Hashimoto ◽  
Takayuki Fujiyoshi ◽  
Takeo Furuya ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Treated Group ◽  
Control Group ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Neuroprotective Effects ◽  
Cord Injury ◽  
Bone Marrow Derived Cells ◽  
Stimulating Factor ◽  
Angiogenic Cytokines

Object Granulocyte colony-stimulating factor (G-CSF) has neuroprotective effects on the CNS. The authors have previously demonstrated that G-CSF also exerts neuroprotective effects in experimental spinal cord injury (SCI) by enhancing migration of bone marrow–derived cells into the damaged spinal cord, increasing glial differentiation of bone marrow–derived cells, enhancing antiapoptotic effects on both neurons and oligodendrocytes, and by reducing demyelination and expression of inflammatory cytokines. Because the degree of angiogenesis in the subacute phase after SCI correlates with regenerative responses, it is possible that G-CSF's neuroprotective effects after SCI are due to enhancement of angiogenesis. The aim of this study was to assess the effects of G-CSF on the vascular system after SCI. Methods A contusive SCI rat model was used and the animals were randomly allocated to either a G-CSF–treated group or a control group. Integrity of the blood–spinal cord barrier was evaluated by measuring the degree of edema in the cord and the volume of extravasation. For histological evaluation, cryosections were immunostained with anti–von Willebrand factor and the number of vessels was counted to assess revascularization. Real-time reverse transcriptase polymerase chain reaction was performed to assess expression of angiogenic cytokines, and recovery of motor function was assessed with function tests. Results In the G-CSF–treated rats, the total number of vessels with a diameter > 20 μm was significantly larger and expression of angiogenic cytokines was significantly higher than those in the control group. The G-CSF–treated group showed significantly greater recovery of hindlimb function than the control group. Conclusions These results suggest that G-CSF exerts neuroprotective effects via promotion of angiogenesis after SCI.

Neuroprotective effects of Nigella sativa on experimental spinal cord injury in rats

2006 ◽  
Vol 25 (3) ◽  
pp. 127-133 ◽  
Author(s):  
M Kanter ◽  
O Coskun ◽  
M Kalayc ◽  
S Buyukbas ◽  
F Cagavi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nigella Sativa ◽  
Protein Carbonyl ◽  
Control Group ◽  
Spinal Cord Tissue ◽  
Neuroprotective Effects ◽  
Tissue Samples ◽  
Experimental Spinal Cord Injury ◽  
Cord Injury

The aim of this study was to investigate the possible beneficial effects of Nigella sativa (NS) in comparison to methylprednisolone on experimental spinal cord injury (SCI) in rats. SCI was performed by placing an aneurysm clip extradurally at the level of T11-12. Rats were neurologically tested over 24 h after trauma and spinal cord tissue samples were harvested for both biochemical and histopathological evaluation. The neurological scores of rats were not found to be different in SCI groups. SCI significantly increased the spinal cord tissue malondialdehyde (MDA) and protein carbonyl (PC) levels, however SCI decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzyme activities compared to the control. Methylprednisolone and NS treatment decreased tissue MDA and PC levels and prevented inhibition of SOD, GSH-Px and CAT enzymes in the tissues. The most significant results were obtained when NS was given. In SCI and placebo groups, the neurons of spinal cord tissue became extensively dark and degenerated with picnotic nuclei. The morphology of neurons in methylprednisolone and NS-treated groups were well protected, however, not as well as the neurons of the control group. The number of neurons in the spinal cord tissue of the SCI and placebo groups was significantly less than the control, laminectomy, methylprednisolone and NS-treated groups. In conclusion, NS treatment might be beneficial in spinal cord tissue damage, and therefore shows potential for clinical implications.

scholarly journals Biological Functions and Therapeutic Potential of Autophagy in Spinal Cord Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Hai-Yang Liao ◽  
Zhi-Qiang Wang ◽  
Rui Ran ◽  
Kai-Sheng Zhou ◽  
Chun-Wei Ma ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Biological Therapy ◽  
Therapeutic Potential ◽  
Degradation Pathway ◽  
Neuroprotective Effects ◽  
Current Review ◽  
Cord Injury ◽  
Evolutionarily Conserved

Autophagy is an evolutionarily conserved lysosomal degradation pathway that maintains metabolism and homeostasis by eliminating protein aggregates and damaged organelles. Many studies have reported that autophagy plays an important role in spinal cord injury (SCI). However, the spatiotemporal patterns of autophagy activation after traumatic SCI are contradictory. Most studies show that the activation of autophagy and inhibition of apoptosis have neuroprotective effects on traumatic SCI. However, reports demonstrate that autophagy is strongly associated with distal neuronal death and the impaired functional recovery following traumatic SCI. This article introduces SCI pathophysiology, the physiology and mechanism of autophagy, and our current review on its role in traumatic SCI. We also discuss the interaction between autophagy and apoptosis and the therapeutic effect of activating or inhibiting autophagy in promoting functional recovery. Thus, we aim to provide a theoretical basis for the biological therapy of SCI.

Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury

2016 ◽  
Vol 25 (1) ◽  
pp. 114-124 ◽  
Author(s):  
Sergiy V. Kushchayev ◽  
Morgan B. Giers ◽  
Doris Hom Eng ◽  
Nikolay L. Martirosyan ◽  
Jennifer M. Eschbacher ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuroprotective Effect ◽  
Scar Tissue ◽  
Treated Group ◽  
Secondary Injury ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Cord Injury ◽  
Behavioral Assessments

OBJECTIVE Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue. METHODS A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel–treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells). RESULTS The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel–treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel–treated group. There was a decreased presence of inflammatory cells in the HA hydrogel–treated group. No axonal or neuronal regeneration was observed. CONCLUSIONS The results of these experiments show that HA hydrogel had a neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold.

scholarly journals Nimodipine alleviates apoptosis-mediated impairments through the mitochondrial pathway after spinal cord injury

2011 ◽  
Vol 57 (3) ◽  
pp. 340-349 ◽  
Author(s):  
Yafei Cai ◽  
Rui Fan ◽  
Tianmiao Hua ◽  
Huiling Liu ◽  
Jing Li
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Caspase 3 ◽  
Treated Group ◽  
Mitochondrial Pathway ◽  
Calcium Flux ◽  
Control Group ◽  
Cord Injury ◽  
Before And After ◽  
Apoptosis Detection

Abstract Spinal cord injury (SCI) remains an unsolved human health challenge. To alleviate the impairments of SCI, we studied the therapeutic effect of nimodipine (an L-type Ca2+ channel antagonist) on functional recovery from SCI using Nystrom’s method in a mouse model. Eighty-four mice were divided into three groups: control group in which only vertebral plates were cut off without causing any spinal injuries; SCI; and SCI with nimodipine treatment. We assessed the histopathology, apoptosis detection, cell cycle, mitochondrial transmembrane potential, bcl-2/bax and caspase-3 levels of tissue 8 h, 1 d, 3 d and 4 d after trauma to evaluate rehabilitation. Behavioral performances were also assessed before and after nimodipine treatment. Results from inclined plane tests, motor score assessment and histological observations indicated that mice in the nimodipine-treated group rehabilitated better than those in the SCI group. The ratio of apoptosis, caspase-3 and bax expression in the nimodipine-treated group were significantly lower than those in the SCI group. The mitochondrial membrane potential and bcl-2 expression were up-regulated in the nimodipine-treated group. Taken together, our results indicate that the inhibition of calcium flux by nimodipine could reduce apoptosis processes and tissue damage through a mitochondrial pathway after spinal cord trauma.

scholarly journals Bazedoxifene, a Selective Estrogen Receptor Modulator, Promotes Functional Recovery in a Spinal Cord Injury Rat Model

2021 ◽  
Vol 22 (20) ◽  
pp. 11012
Author(s):  
Yiyoung Kim ◽  
Eun Ji Roh ◽  
Hari Prasad Joshi ◽  
Hae Eun Shin ◽  
Hyemin Choi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Therapeutic Potential ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Sprague Dawley ◽  
Post Injury ◽  
Static Compression ◽  
Cord Injury

In research on various central nervous system injuries, bazedoxifene acetate (BZA) has shown two main effects: neuroprotection by suppressing the inflammatory response and remyelination by enhancing oligodendrocyte precursor cell differentiation and oligodendrocyte proliferation. We examined the effects of BZA in a rat spinal cord injury (SCI) model. Anti-inflammatory and anti-apoptotic effects were investigated in RAW 264.7 cells, and blood-spinal cord barrier (BSCB) permeability and angiogenesis were evaluated in a human brain endothelial cell line (hCMEC/D3). In vivo experiments were carried out on female Sprague Dawley rats subjected to moderate static compression SCI. The rats were intraperitoneally injected with either vehicle or BZA (1mg/kg pre-SCI and 3mg/kg for 7 days post-SCI) daily. BZA decreased the lipopolysaccharide-induced production of proinflammatory cytokines and nitric oxide in RAW 264.7 cells and preserved BSCB disruption in hCMEC/D3 cells. In the rats, BZA reduced caspase-3 activity at 1 day post-injury (dpi) and suppressed phosphorylation of MAPK (p38 and ERK) at dpi 2, hence reducing the expression of IL-6, a proinflammatory cytokine. BZA also led to remyelination at dpi 20. BZA contributed to improvements in locomotor recovery after compressive SCI. This evidence suggests that BZA may have therapeutic potential to promote neuroprotection, remyelination, and functional outcomes following SCI.

Human Mesenchymal Stem Cells for Spinal Cord Injury

2020 ◽  
Vol 15 (4) ◽  
pp. 340-348 ◽  
Author(s):  
Masoumeh Alishahi ◽  
Amir Anbiyaiee ◽  
Maryam Farzaneh ◽  
Seyed E. Khoshnam
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Therapeutic Option ◽  
Human Mscs ◽  
Multipotent Stem Cells ◽  
Cord Injury

Spinal Cord Injury (SCI), as a devastating and life-altering neurological disorder, is one of the most serious health issues. Currently, the management of acute SCI includes pharmacotherapy and surgical decompression. Both the approaches have been observed to have adverse physiological effects on SCI patients. Therefore, novel therapeutic targets for the management of SCI are urgently required for developing cell-based therapies. Multipotent stem cells, as a novel strategy for the treatment of tissue injury, may provide an effective therapeutic option against many neurological disorders. Mesenchymal stem cells (MSCs) or multipotent stromal cells can typically self-renew and generate various cell types. These cells are often isolated from bone marrow (BM-MSCs), adipose tissues (AD-MSCs), umbilical cord blood (UCB-MSCs), and placenta (PMSCs). MSCs have remarkable potential for the development of regenerative therapies in animal models and humans with SCI. Herein, we summarize the therapeutic potential of human MSCs in the treatment of SCI.

scholarly journals Study of Effect of Salvianolic Acid B on Motor Function Recovery in Rats with Spinal Cord Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Chong Xun ◽  
Yang Hu ◽  
Ming Lu ◽  
Shouyu Wang ◽  
Decheng Lv
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Treated Group ◽  
Salvianolic Acid B ◽  
Control Group ◽  
Western Blots ◽  
Salvianolic Acid ◽  
Function Recovery ◽  
Cord Injury

In this study effect of salvianolic acid B was observed on motor function recovery of rats with spinal cord injury. 50 rats were selected and after inducing SCI their recovery under controlled conditions was studied using Sal B and PBS (as control). Both compounds were introduced intraperitoneally in respective groups of traumatic rats at the same time intervals for 28 days. It was observed that Sal B introduced at 5  mg/kg/day resulted in better motor function recovery. BBB score was recorded which increased significantly along with the reduction in cavity area observed by bright field microscopy of tissues, that is, from 1 to 10 and from0.20±0.05 mm2to0.10±0.03 mm2, in Sal B treated group, respectively, compared to PBS group. Statistical analysis was carried out using SPSS software (SPSS, Chicago, IL, USA), values were expressed as mean ± SEM, andPvalue <0.01 was considered significant. Effect of Sal B on expression of NF-kB p65 and IkBαwas studied and OD values of densitometry of western blots were taken. MPO activity was also studied. It was observed that treatment of Sal B significantly reduced the expression of both compounds in Sal B treated group as compared to control group after 28 days of treatment.

scholarly journals Therapeutic potential of flavonoids in spinal cord injury

2017 ◽  
Vol 28 (1) ◽  
pp. 87-101 ◽  
Author(s):  
Peng Zhang ◽  
Christian Hölscher ◽  
Xun Ma
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Therapeutic Potential ◽  
Economic Effects ◽  
Pharmacological Properties ◽  
Plant Metabolites ◽  
Neuroprotective Effects ◽  
Cord Injury ◽  
Anti Oxidant ◽  
Novel Therapeutic Strategies

AbstractSpinal cord injury (SCI) is a catastrophic event that can profoundly affect a patient’s life, with far-reaching social and economic effects. A consequential sequence of SCI is the significant neurological or psychological deficit, which obviously contributes to the overall burden of this condition. To date, there is no effective treatment for SCI. Therefore, developing novel therapeutic strategies for SCI is highly prioritized. Flavonoids, one of the most numerous and ubiquitous groups of plant metabolites, are the active ingredients of traditional Chinese medicine such as Scutellaria baicalensis Georgi (Huang Qin) or Ginkgo biloba (Ying Xin). Accumulated research data show that flavonoids possess a range of key pharmacological properties such as anti-inflammatory, anti-oxidant, anti-tumor, anti-viral, anti-cardiovascular disease, immunomodulatory, and neuroprotective effects. Based on this, the flavonoids show therapeutic potential for SCI diseases. In this paper, we will review the pharmacological properties of different types of flavonoids for the treatment of SCI diseases, and potential underlying biochemical mechanisms of action will also be described.

Stem Cell Transplantation: A Promising Therapy for Spinal Cord Injury

2020 ◽  
Vol 15 (4) ◽  
pp. 321-331 ◽  
Author(s):  
Zhe Gong ◽  
Kaishun Xia ◽  
Ankai Xu ◽  
Chao Yu ◽  
Chenggui Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Current Status ◽  
Cord Injury

Spinal Cord Injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced Pluripotent Stem Cells (iPSCs), Embryonic Stem Cells (ESCs), Mesenchymal Stem Cells (MSCs) and Neural Progenitor Cells (NPCs) /Neural Stem Cells (NSCs) have therapeutic potential for SCI. However, the efficacy and safety of these stem cellbased therapy for SCI remain controversial. In this review, we introduce the pathogenesis of SCI, summarize the current status of the application of these stem cells in SCI repair, and discuss possible mechanisms responsible for functional recovery of SCI after stem cell transplantation. Finally, we highlight several areas for further exploitation of stem cells as a promising regenerative therapy of SCI.

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