scholarly journals Local Delivery of β-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury

2018 ◽  
Vol 49 (2) ◽  
pp. 595-609 ◽  
Author(s):  
Jingyu Wang ◽  
Heyangzi Li ◽  
Yucheng Ren ◽  
Ying Yao ◽  
Jue Hu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Rat Model ◽  
Neuronal Apoptosis ◽  
Ventral Horn ◽  
Tunel Staining ◽  
Cord Injury

Background/Aims: Spinal cord injury (SCI) is a serious global problem that leads to permanent motor and sensory deficits. This study explores the anti-apoptotic and neuroprotective effects of the natural extract β-elemene in vitro and in a rat model of SCI. Methods: CCK-8 assay was used to evaluate cell viability and lactate dehydrogenase assay was used to evaluate cytotoxicity. A model of cell injury was established using cobalt chloride. Apoptosis was evaluated using a fluorescence-activated cell sorting assay of annexin V-FITC and propidium iodide staining. A rat SCI model was created via the modified Allen’s method and Basso, Beattie, and Bresnahan (BBB) scores were used to assess locomotor function. Inflammatory responses were assessed via enzyme-linked immunosorbent assay (ELISA). Apoptotic and surviving neurons in the ventral horn were respectively observed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining. Western blotting was used to measure protein expression. Results: β-elemene (20 μg/ml) promoted cell viability by activating phosphorylation of the PI3K-AKT-mTOR pathway. β-elemene reduced CoCl2-induced cellular death and apoptosis by suppressing the expression levels of CHOP, cleaved-caspase 12, 78-kilodalton glucose-regulated protein, cleaved-caspase 3, and the Bax/Bcl-2 ratio. In the rat model of SCI, Nissl and TUNEL staining showed that β-elemene promoted motor neuron survival and reduced neuronal apoptosis in the spinal cord ventral horn. BBB scores showed that β-elemene significantly promoted locomotor behavioral recovery after SCI. In addition, β-elemene reduced the ELISA-detected secretion of interleukin (IL)-6 and IL-1β. Conclusion: β-elemene reduces neuronal apoptosis by alleviating endoplasmic reticulum stress in vitro and in vivo. In addition, β-elemene promotes locomotor function recovery and tissue repair in SCI rats. Thus, our study provides a novel encouraging strategy for the potential treatment of β-elemene in SCI patients.

scholarly journals A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2245
Author(s):  
Jue-Zong Yeh ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Yi-Wen Wang ◽  
Gang-Yi Fan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Neural Plasticity ◽  
Collagen Scaffold ◽  
Glial Scar ◽  
Beneficial Effects ◽  
Cord Injury

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

Deletion of Endoplasmic Reticulum Stress-Induced CHOP Protects Microvasculature Post-Spinal Cord Injury

2012 ◽  
Vol 9 (4) ◽  
pp. 274-281 ◽  
Author(s):  
Janelle M. Fassbender ◽  
Sujata Saraswat-Ohri ◽  
Scott A. Myers ◽  
Mark J. Gruenthal ◽  
Richard L. Benton ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cord Injury

scholarly journals Small extracellular vesicles encapsulating CCL2 from activated astrocytes induce microglial activation and neuronal apoptosis after traumatic spinal cord injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuluo Rong ◽  
Chengyue Ji ◽  
Zhuanghui Wang ◽  
Xuhui Ge ◽  
Jiaxing Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Extracellular Vesicles ◽  
Neuronal Apoptosis ◽  
Microglial Activation ◽  
Neuronal Cells ◽  
Cell Communication ◽  
Bioactive Lipids ◽  
Cord Injury

Abstract Background Spinal cord injury (SCI) is a severe traumatic disease which causes high disability and mortality rates. The molecular pathological features after spinal cord injury mainly involve the inflammatory response, microglial and neuronal apoptosis, abnormal proliferation of astrocytes, and the formation of glial scars. However, the microenvironmental changes after spinal cord injury are complex, and the interactions between glial cells and nerve cells remain unclear. Small extracellular vesicles (sEVs) may play a key role in cell communication by transporting RNA, proteins, and bioactive lipids between cells. Few studies have examined the intercellular communication of astrocytes through sEVs after SCI. The inflammatory signal released from astrocytes is known to initiate microglial activation, but its effects on neurons after SCI remain to be further clarified. Methods Electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were applied to characterize sEVs. We examined microglial activation and neuronal apoptosis mediated by astrocyte activation in an experimental model of acute spinal cord injury and in cell culture in vitro. Results Our results indicated that astrocytes activated after spinal cord injury release CCL2, act on microglia and neuronal cells through the sEV pathway, and promote neuronal apoptosis and microglial activation after binding the CCR2. Subsequently, the activated microglia release IL-1β, which acts on neuronal cells, thereby further aggravating their apoptosis. Conclusion This study elucidates that astrocytes interact with microglia and neurons through the sEV pathway after SCI, enriching the mechanism of CCL2 in neuroinflammation and spinal neurodegeneration, and providing a new theoretical basis of CCL2 as a therapeutic target for SCI.

Necrostatin-1 Mitigates Endoplasmic Reticulum Stress After Spinal Cord Injury

2017 ◽  
Vol 42 (12) ◽  
pp. 3548-3558 ◽  
Author(s):  
Shuang Wang ◽  
Jin Wu ◽  
Yu-Zhe Zeng ◽  
Song-Song Wu ◽  
Guo-Rong Deng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cord Injury
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