scholarly journals Inhibition of TGF-β repairs spinal cord injury by attenuating EphrinB2 expressing through inducing miR-484 from fibroblast

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dayu Pan ◽  
Fuhan Yang ◽  
Shibo Zhu ◽  
Yongjin Li ◽  
Guangzhi Ning ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Axon Growth ◽  
Neutralizing Antibody ◽  
Mapk Signaling ◽  
Sensory Function ◽  
Systemic Injection ◽  
Cord Injury ◽  
Fibrotic Scar

AbstractSpinal cord injury (SCI) can lead to severe loss of motor and sensory function with high disability and mortality. The effective treatment of SCI remains unknown. Here we find systemic injection of TGF-β neutralizing antibody induces the protection of axon growth, survival of neurons, and functional recovery, whereas erythropoietin-producing hepatoma interactor B2 (EphrinB2) expression and fibroblasts distribution are attenuated. Knockout of TGF-β type II receptor in fibroblasts can also decrease EphrinB2 expression and improve spinal cord injury recovery. Moreover, miR-488 was confirmed to be the most upregulated gene related to EphrinB2 releasing in fibroblasts after SCI and miR-488 initiates EphrinB2 expression and physical barrier building through MAPK signaling after SCI. Our study points toward elevated levels of active TGF-β as inducer and promoters of fibroblasts distribution, fibrotic scar formation, and EphrinB2 expression, and deletion of global TGF-β or the receptor of TGF-β in Col1α2 lineage fibroblasts significantly improve functional recovery after SCI, which suggest that TGF-β might be a therapeutic target in SCI.

scholarly journals Combined Treatment with Fasudil and Menthol Improves Functional Recovery in Rat Spinal Cord Injury Model

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 258
Author(s):  
JeongHoon Kim ◽  
Hari Prasad Joshi ◽  
Kyoung-Tae Kim ◽  
Yi Young Kim ◽  
Keundong Yeo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Combined Treatment ◽  
Scar Formation ◽  
Sprague Dawley ◽  
Static Compression ◽  
Cord Injury ◽  
Fibrotic Scar ◽  
Spinal Cord Dysfunction

Neuroprotective measures by preventing secondary spinal cord injury (SCI) are one of the main strategies for repairing an injured spinal cord. Fasudil and menthol may be potent neuroprotective agents, which act by inhibiting a rho-associated protein kinase (ROCK) and suppressing the inflammatory response, respectively. We hypothesized that combined treatment of fasudil and menthol could improve functional recovery by decreasing inflammation, apoptosis, and glial scar formation. We tested our hypothesis by administering fasudil and menthol intraperitoneally (i.p.) to female Sprague Dawley rats after moderate static compression (35 g of impounder for 5 min) of T10 spinal cord. The rats were randomly divided into five experimental groups: (i) sham animals received laminectomy alone, (ii) injured (SCI) and untreated (saline 0.2 mL/day, i.p.) rats, (iii) injured (SCI) rats treated with fasudil (10 mg/kg/day, i.p.) for two weeks, (iv) injured (SCI) rats treated with menthol (10 mg/kg/day, i.p.) for twoweeks, (v) injured (SCI) rats treated with fasudil (5 mg/kg/day, i.p.) and menthol (10 mg/kg/day, i.p.) for two weeks. Compared to single treatment groups, combined treatment of fasudil and menthol demonstrated significant functional recovery and pain amelioration, which, thereby, significantly reduced inflammation, apoptosis, and glial/fibrotic scar formation. Therefore, combined treatment of fasudil and menthol may provide effective amelioration of spinal cord dysfunction by a synergistic effect of fasudil and menthol.

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

scholarly journals Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniel J. Hellenbrand ◽  
Charles M. Quinn ◽  
Zachariah J. Piper ◽  
Carolyn N. Morehouse ◽  
Jordyn A. Fixel ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Immune Cell ◽  
Sensory Function ◽  
Glutamate Excitotoxicity ◽  
Secondary Injury ◽  
Extensive Literature ◽  
Secondary Damage ◽  
Cord Injury

AbstractTraumatic spinal cord injury (SCI) is a devastating neurological condition that results in a loss of motor and sensory function. Although extensive research to develop treatments for SCI has been performed, to date, none of these treatments have produced a meaningful amount of functional recovery after injury. The primary injury is caused by the initial trauma to the spinal cord and results in ischemia, oxidative damage, edema, and glutamate excitotoxicity. This process initiates a secondary injury cascade, which starts just a few hours post-injury and may continue for more than 6 months, leading to additional cell death and spinal cord damage. Inflammation after SCI is complex and driven by a diverse set of cells and signaling molecules. In this review, we utilize an extensive literature survey to develop the timeline of local immune cell and cytokine behavior after SCI in rodent models. We discuss the precise functional roles of several key cytokines and their effects on a variety of cell types involved in the secondary injury cascade. Furthermore, variations in the inflammatory response between rats and mice are highlighted. Since current SCI treatment options do not successfully initiate functional recovery or axonal regeneration, identifying the specific mechanisms attributed to secondary injury is critical. With a more thorough understanding of the complex SCI pathophysiology, effective therapeutic targets with realistic timelines for intervention may be established to successfully attenuate secondary damage.

Promoting Axonal Extension and Repair After Spinal Cord Injury by Inhibiting the Expression of Rho Gene Based on RNA Interference

2020 ◽  
Vol 10 (7) ◽  
pp. 1046-1051
Author(s):  
Bo Yu ◽  
Hongmei Zhang ◽  
Jun Hong ◽  
Yonggang Lu ◽  
Yajun Zhang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Real Time ◽  
Real Time Pcr ◽  
Average Length ◽  
Axon Growth ◽  
Sensory Function ◽  
Control Group ◽  
Central Nervous System Damage ◽  
Cord Injury

Spinal cord injury causes central nervous system damage. Rho inhibits axonal regeneration. This study is intended to analyze the effect of inhibition of Rho expression on axonal repair. The oligodendrocytes were isolated and divided into NC group and shRNA-RhoA group followed by analysis of the average length of axon growth and average microtubule fluorescence density by immunofluorescence, Nogo, MAG and RhoA expression were by Real time PCR. Wistar rats were separated into control group; SCI group and shRNA-RhoA group followed by analysis of the BBB scores and the Reuter score of sensory function, RhoA expression by Real time PCR and Western blot, Caspase3 activity as well as Nogo and MAG expression by Real time PCR. Compared with NC group, shRNA-RhoA group showed significantly increased average length of axon growth and average microtubule fluorescence density at the distal axon and reduced expression of RhoA, Nogo and MAG (P < 0 05). In comparison to control group, SCI group presented significantly increased RhoA expression, decreased BBB score, increased Reuter score and Caspase3 activity as well as elevated Nogo and MAG expression (P < 0 05). The shRNA-RhoA group significantly decreased RhoA expression, increased BBB score, decreased Reuter score and Caspase3 activity, and reduced Nogo and MAG expression compared with SCI group (P < 0 05). Inhibiting RhoA expression can promote axon extension and regenerative repair. Targeting RhoA reduces axon growth inhibitory factor expression, inhibits apoptosis and effectively alleviates SCI.

scholarly journals Proliferating NG2-Cell-Dependent Angiogenesis and Scar Formation Alter Axon Growth and Functional Recovery After Spinal Cord Injury in Mice

2017 ◽  
Vol 38 (6) ◽  
pp. 1366-1382 ◽  
Author(s):  
Zoe C. Hesp ◽  
Rim Y. Yoseph ◽  
Ryusuke Suzuki ◽  
Peter Jukkola ◽  
Claire Wilson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Axon Growth ◽  
Scar Formation ◽  
Cord Injury

scholarly journals GSK-3 Inhibitor Promotes Neuronal Cell Regeneration and Functional Recovery in a Rat Model of Spinal Cord Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Fei Lei ◽  
Wen He ◽  
Xinggui Tian ◽  
Qingzhong Zhou ◽  
Lipeng Zheng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Glycogen Synthase ◽  
Neuronal Cell ◽  
Axon Growth ◽  
Competitive Inhibitor ◽  
Lower Limbs ◽  
Cell Regeneration ◽  
Cord Injury

The reparative process following spinal cord injury (SCI) is extremely complicated. Cells in the microenvironment express multiple inhibitory factors that affect axonal regeneration over a prolonged period of time. The axon growth inhibitory factor glycogen synthase kinase-3 (GSK-3) is an important factor during these processes. TDZD-8 (4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione) is the most effective and specific non-ATP-competitive inhibitor of GSK-3. Here, we show that administering TDZD-8 after SCI was associated with significantly inhibited neuronal apoptosis, upregulated GAP-43 expression, increased density of cortical spinal tract fibers around areas of injury, and increased Basso, Beattie, and Bresnahan (BBB) scores in the lower limbs. These findings support the notion that GSK-3 inhibitors promote neuronal cell regeneration and lower limb functional recovery.

scholarly journals The effect of systemic PTEN antagonist peptides on axon growth and functional recovery after spinal cord injury

Biomaterials ◽  
2014 ◽  
Vol 35 (16) ◽  
pp. 4610-4626 ◽  
Author(s):  
Yosuke Ohtake ◽  
Dongsun Park ◽  
P.M. Abdul-Muneer ◽  
Hui Li ◽  
Bin Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Axon Growth ◽  
Antagonist Peptides ◽  
Cord Injury

scholarly journals Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Hisao Miyajima ◽  
Takahide Itokazu ◽  
Shogo Tanabe ◽  
Toshihide Yamashita
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Proliferation ◽  
Functional Recovery ◽  
Neurotrophic Factors ◽  
Ependymal Cell ◽  
Neutralizing Antibody ◽  
Conditional Knockout ◽  
Ependymal Cells ◽  
Cord Injury

AbstractEpendymal cells have been suggested to act as neural stem cells and exert beneficial effects after spinal cord injury (SCI). However, the molecular mechanism underlying ependymal cell regulation after SCI remains unknown. To examine the possible effect of IL-17A on ependymal cell proliferation after SCI, we locally administrated IL-17A neutralizing antibody to the injured spinal cord of a contusion SCI mouse model, and revealed that IL-17A neutralization promoted ependymal cell proliferation, which was paralleled by functional recovery and axonal reorganization of both the corticospinal tract and the raphespinal tract. Further, to test whether ependymal cell-specific manipulation of IL-17A signaling is enough to affect the outcomes of SCI, we generated ependymal cell-specific conditional IL-17RA-knockout mice and analyzed their anatomical and functional response to SCI. As a result, conditional knockout of IL-17RA in ependymal cells enhanced both axonal growth and functional recovery, accompanied by an increase in mRNA expression of neurotrophic factors. Thus, Ependymal cells may enhance the regenerative process partially by secreting neurotrophic factors, and IL-17A stimulation negatively regulates this beneficial effect. Molecular manipulation of ependymal cells might be a viable strategy for improving functional 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.

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