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 Peripheral Nerve-Derived Stem Cell Spheroids Induce Functional Recovery and Repair after Spinal Cord Injury in Rodents

2021 ◽  
Vol 22 (8) ◽  
pp. 4141
Author(s):  
Hye-Lan Lee ◽  
Chung-Eun Yeum ◽  
Hye-Yeong Lee ◽  
Jinsoo Oh ◽  
Jong-Tae Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Growth Factor ◽  
Peripheral Nerve ◽  
Neural Crest ◽  
Functional Recovery ◽  
Neurotrophic Factors ◽  
Cord Injury

Stem cell therapy is one of the most promising candidate treatments for spinal cord injury. Research has shown optimistic results for this therapy, but clinical limitations remain, including poor viability, engraftment, and differentiation. Here, we isolated novel peripheral nerve-derived stem cells (PNSCs) from adult peripheral nerves with similar characteristics to neural-crest stem cells. These PNSCs expressed neural-crest specific markers and showed multilineage differentiation potential into Schwann cells, neuroglia, neurons, and mesodermal cells. In addition, PNSCs showed therapeutic potential by releasing the neurotrophic factors, including glial cell-line-derived neurotrophic factor, insulin-like growth factor, nerve growth factor, and neurotrophin-3. PNSC abilities were also enhanced by their development into spheroids which secreted neurotrophic factors several times more than non-spheroid PNSCs and expressed several types of extra cellular matrix. These features suggest that the potential for these PNSC spheroids can overcome their limitations. In an animal spinal cord injury (SCI) model, these PNSC spheroids induced functional recovery and neuronal regeneration. These PNSC spheroids also reduced the neuropathic pain which accompanies SCI after remyelination. These PNSC spheroids may represent a new therapeutic approach for patients suffering from SCI.

Ependymal cell proliferation after spinal cord injury

1987 ◽  
Vol 28 (5) ◽  
pp. 401 ◽  
Author(s):  
Jesús Vaquero ◽  
Maria Jose Ramiro ◽  
Santiago Oya ◽  
Jose Manuel Cabezudo
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Proliferation ◽  
Ependymal Cell ◽  
Cord Injury

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 Allogeneic Neural Stem Cell Transplant Promotes Functional Recovery of Locomotion After Complete Transected Spinal Cord Injury Predominantly by Secreting Neurotrophic Factors

2021 ◽  
Author(s):  
Shuo Liu ◽  
Caixia Fan ◽  
Yuanyuan Xie ◽  
Liudi Wang ◽  
Yanyan Cui ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Neurotrophic Factors ◽  
Culture Medium ◽  
Collagen Scaffold ◽  
Locomotor Recovery ◽  
Cord Injury ◽  
Neuronal Replacement

Abstract ObjectiveCell-based therapy is a promising strategy for spinal cord injury (SCI) repair, but faced the challenges to direct the neuronal differentiation of appropriate neuron subtypes for achieving the neuronal replacement. We investigated whether allogeneic beforehand in vitro differentiated neural stem cells (NSCs) could relieve the adverse effects of regeneration inhibitory niche and promote motor functional recovery by accomplishing neuronal replacement after transplant into SCI rats. MethodsCollagen scaffold combined with digested NSCs, NSC sphere, differentiated neurons, and sphere of differentiated neurons were transplanted into completely transected SCI in rats and therapeutic outcomes were investigated. Next, we enriched complex of neurotrophic factors secreted from culture medium of NSCs, neurons, and sphere of neurons and a total of 2 mg total enriched protein combined with collagen scaffold were transplanted into SCI to further assay whether allogeneic NSCs transplant promotes the recovery of SCI predominantly by secreting neurotrophic factors. ResultsNSCs differentiated into neurons in density-dependent manner in vitro and sphere of NSCs could counteract myelin-induced inhibition of neuronal differentiation. Collagen scaffold combined with digested NSCs, NSC sphere, differentiated neurons, and sphere of differentiated neurons were transplanted into completely transected SCI in rats. Overall the cell treatment groups had a much better locomotor recovery, tissue remodeling, and newborn neuron formation than alone collagen scaffold treatment, compared with alone collagen material transplant and control group. However, unexpectedly, the differentiated cell treatment (differentiated neurons and sphere of differentiated neurons transplants) did not present striking better locomotor recovery than the undifferentiated NSCs and sphere of NSCs treatments, only sphere of neurons showed a slight increase in BBB score compared to other cell treatments. Next, we enriched complex of neurotrophic factors secreted from culture medium of NSCs, neurons, and sphere of neurons. BBB score analysis showed that the secreted neurotrophic factors from NSCs, neurons, and sphere of neurons would promote functional recovery of SCI to the same extent. ConclusionAllogeneic NSCs transplant promotes functional recovery of SCI predominantly by secreting neurotrophic factors, not direct neuronal replacement of differentiated neurons from transplanted cells.

scholarly journals Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury

2020 ◽  
Vol 11 ◽  
Author(s):  
Roxana Rodríguez-Barrera ◽  
Adrián Flores-Romero ◽  
Vinnitsa Buzoianu-Anguiano ◽  
Elisa Garcia ◽  
Karla Soria-Zavala ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Combination Strategy ◽  
Chronic Spinal Cord Injury ◽  
Cord Injury

scholarly journals Exercise Ameliorates Spinal Cord Injury by Changing DNA Methylation

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 143
Author(s):  
Ganchimeg Davaa ◽  
Jin Young Hong ◽  
Tae Uk Kim ◽  
Seong Jae Lee ◽  
Seo Young Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Treadmill Exercise ◽  
Exercise Group ◽  
Control Group ◽  
Epigenetic Changes ◽  
Cord Injury ◽  
The Brain

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.

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