scholarly journals Exosome-Mediated siRNA pool Inhibits Axonal Growth Inhibitor in Cortical Neurons of Spinal Cord Injury in Rats

2020 ◽  
Author(s):  
Qi Liao ◽  
Jiang-Hua Ming ◽  
Ge-Liang Hu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Proliferation ◽  
Cortical Neurons ◽  
Axon Growth ◽  
Axonal Growth ◽  
Growth Inhibitor ◽  
Protective Role ◽  
Primary Cortical Neurons ◽  
Cord Injury

Abstract Background: As exosomes have been confirmed as a reservoir of siRNAs involved in certain diseases, the current study aims to investigate whether exosomal-siRNA could exert a protective role in spinal cord injury (SCI). Methods and Results: Exosomes in our experiment were isolated from lysosomal membrane-associated protein 2b (Lamp2b) overexpression HEK 293T cells, and purity of exosomes was characterized by the expression of CD9, CD47, and CD63 via western blot. Furthermore, the siRNA pool contains four siRNAs including siRNA-NgR, siRNA-LINGO-1, siRNA-Troy, and siRNA-PTEN was loaded to the exosomes, which indicated a significant role for the siRNA pool in reducing the expression of axon growth inhibitory factors. Upon the completion of loading into exosomes (exo-siRNA pool), the exo-siRNA pool was injected into primary cortical neurons of the SCI model in rats before cell proliferation and Rho expression were determined With the results revealed that purified addition could be applied to future experiments. The exo-siRNA pooled transfection caused downregulation of axon growth suppressors in primary cortical neurons including Nogo receptors (NgR), leucine-rich repeats and immunoglobulin domain-containing protein 1 (LINGO-1), Troy, and phosphatase and tenson homolog (PTEN). Cell proliferation and Rho expression of primary cortical neurons inhibited the expression of axonal growth inhibitors in rats with SCI by transfecting exogenous Sirna. Conclusion: This study confirmed that exosomes derived from Lamp2b overexpression HEK 293T cells facilitated both the recovery of functions and the survival of neurons when being loaded with the siRNA pool.

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 Bone Marrow Mesenchymal Stem Cell-Derived Exosome-Educated Macrophages Promote Functional Healing After Spinal Cord Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Chengjun Li ◽  
Tian Qin ◽  
Jinyun Zhao ◽  
Rundong He ◽  
Haicheng Wen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cortical Neurons ◽  
Axon Growth ◽  
Sensory Function ◽  
Functional Assay ◽  
Cord Injury

The spinal cord injury is a site of severe central nervous system (CNS) trauma and disease without an effective treatment strategy. Neurovascular injuries occur spontaneously following spinal cord injury (SCI), leading to irreversible loss of motor and sensory function. Bone marrow mesenchymal stem cell (BMSC)–derived exosome-educated macrophages (EEM) have great characteristics as therapeutic candidates for SCI treatment. It remains unknown whether EEM could promote functional healing after SCI. The effect of EEM on neurovascular regeneration after SCI needs to be further explored. We generated M2-like macrophages using exosomes isolated from BMSCs, which were known as EEM, and directly used these EEM for SCI treatment. We aimed to investigate the effects of EEM using a spinal cord contusive injury mouse model in vivo combined with an in vitro cell functional assay and compared the results to those of a normal spinal cord without any biological intervention, or PBS treatment or macrophage alone (MQ). Neurological function measurements and histochemical tests were performed to evaluate the effect of EEM on angiogenesis and axon regrowth. In the current study, we found that treatment with EEM effectively promoted the angiogenic activity of HUVECs and axonal growth in cortical neurons. Furthermore, exogenous administration of EEM directly into the injured spinal cord could promote neurological functional healing by modulating angiogenesis and axon growth. EEM treatment could provide a novel strategy to promote healing after SCI and various other neurovascular injury disorders.

scholarly journals Correlation of Nogo A release with glia scar formation in spinal cord injury

2021 ◽  
Vol 10 (6) ◽  
pp. e25410615688
Author(s):  
Juliana Casanovas de Carvalho ◽  
César Augusto Abreu-Pereira ◽  
Lucas Cauê da Silva Assunção ◽  
Rosana Costa Casanovas ◽  
Ana Lucia Abreu-Silva ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Injuries ◽  
Axonal Growth ◽  
Growth Inhibitor ◽  
Glial Scar ◽  
Time Interval ◽  
Cord Injury ◽  
Female Wistar Rats ◽  
Epidural Compression

Several axonal growth inhibitors have already been identified following spinal cord injury, the most known being myelin-derived proteins, such as Nogo-A. The present study aimed to correlate the formation of glial scar with the beginning of growth inhibitor, Nogo-A, release in rats previously submitted to compressive spinal cord injury. For this, 12 male and female Wistar rats (250 ± 50g) were divided into 3 groups of 4 animals each, according to the animals' euthanasia time after spinal cord injury (G3 - three days; G5 - five days; G7 - seven days). Spinal cord injuries were induced by means of dorsal laminectomy of the T10 vertebra and epidural compression. Histopathological evaluation and immunoreactivity of the Nogo-A axonal growth inhibitor were performed. It was observed that there was the release of the axonal inhibitor Nogo-A after 24h after the occurrence of spinal cord injury, and that the glial scar must be maintained, in this time interval, in order to guarantee the rebalancing of the post-trauma environment. Thus, it is suggested that the glial scar should be maintained in the acute phase of the lesion, guaranteeing its numerous benefits for the rebalancing of the post-injured environment and, after 24 hours, when the release of the studied axonal growth inhibitor begins, it should be removed.

scholarly journals Depolarization and electrical stimulation enhance in vitro and in vivo sensory axon growth after spinal cord injury

2018 ◽  
Vol 300 ◽  
pp. 247-258 ◽  
Author(s):  
Ioana Goganau ◽  
Beatrice Sandner ◽  
Norbert Weidner ◽  
Karim Fouad ◽  
Armin Blesch
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Electrical Stimulation ◽  
Axon Growth ◽  
Sensory Axon ◽  
Cord Injury

Protective role of β-carotene against oxidative stress and neuroinflammation in a rat model of spinal cord injury

2018 ◽  
Vol 61 ◽  
pp. 92-99 ◽  
Author(s):  
Lihui Zhou ◽  
Lian Ouyang ◽  
Shuangzhi Lin ◽  
Song Chen ◽  
YingJie Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Protective Role ◽  
Cord Injury ◽  
Β Carotene

scholarly journals An In Vitro Comparison of the Neurotrophic and Angiogenic Activity of Human and Canine Adipose-Derived Mesenchymal Stem Cells (MSCs): Translating MSC-Based Therapies for Spinal Cord Injury

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1301
Author(s):  
Ibtesam R. T. Al Delfi ◽  
Chelsea R. Wood ◽  
Louis D. V. Johnson ◽  
Martyn D. Snow ◽  
John F. Innes ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Proliferation ◽  
Endothelial Cell ◽  
Neuronal Cell ◽  
Endothelial Cell Migration ◽  
Differentiation Potential ◽  
Angiogenic Activity ◽  
Cord Injury

The majority of research into the effects of mesenchymal stem cell (MSC) transplants on spinal cord injury (SCI) is performed in rodent models, which may help inform on mechanisms of action, but does not represent the scale and wound heterogeneity seen in human SCI. In contrast, SCI in dogs occurs naturally, is more akin to human SCI, and can be used to help address important aspects of the development of human MSC-based therapies. To enable translation to the clinic and comparison across species, we have examined the paracrine, regenerative capacity of human and canine adipose-derived MSCs in vitro. MSCs were initially phenotyped according to tissue culture plastic adherence, cluster of differentiation (CD) immunoprofiling and tri-lineage differentiation potential. Conditioned medium (CM) from MSC cultures was then assessed for its neurotrophic and angiogenic activity using established cell-based assays. MSC CM significantly increased neuronal cell proliferation, neurite outgrowth, and βIII tubulin immunopositivity. In addition, MSC CM significantly increased endothelial cell migration, cell proliferation and the formation of tubule-like structures in Matrigel assays. There were no marked or significant differences in the capacity of human or canine MSC CM to stimulate neuronal cell or endothelial cell activity. Hence, this study supports the use of MSC transplants for canine SCI; furthermore, it increases understanding of how this may subsequently provide useful information and translate to MSC transplants for human SCI.

Wnt-Ryk Signaling Mediates Axon Growth Inhibition and Limits Functional Recovery after Spinal Cord Injury

2009 ◽  
Vol 26 (7) ◽  
pp. 955-964 ◽  
Author(s):  
Tomohiro Miyashita ◽  
Masao Koda ◽  
Keiko Kitajo ◽  
Masashi Yamazaki ◽  
Kazuhisa Takahashi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Inhibition ◽  
Functional Recovery ◽  
Axon Growth ◽  
Cord Injury
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