scholarly journals Plant Scaffolds Support Motor Recovery and Regeneration in Rats after Traumatic Spinal Cord Injury

2020 ◽  
Author(s):  
Daniel J. Modulevsky ◽  
Charles M. Cuerrier ◽  
Maxime Leblanc-Latour ◽  
Ryan J. Hickey ◽  
Ras-Jeevan K. Obhi ◽  
...  

ABSTRACTAs of yet, no standard of care incorporates the use of a biomaterial to treat traumatic spinal cord injury (SCI)1–5. However, intense development of biomaterials for treating SCI have focused on the fabrication of microscale channels to support the regrowth of axons while minimizing scar tissue formation6–10. We previously demonstrated that plant tissues can be decellularized and processed to form sterile, biocompatible and implantable biomaterials that support cell infiltration and vascularization in vivo11–13. Notably, the vascular bundles of plant tissues are also composed of microscale channels with geometries thought to be relevant for supporting neural tissue regeneration9,14. We hypothesized that decellularized vascular bundles would support neural regeneration and the recovery of motor function. Therefore, rats which received a complete T8-T9 spinal cord transection were implanted with plant-derived channeled scaffolds. Animals which received the scaffolds alone, with no therapeutic stem cells or other interventions, demonstrated a significant and stable improvement in motor function over six months compared to controls. Histological analysis reveals minimal scarring and axonal regrowth through the scaffolds, further confirmed with tracer studies. Taken together, our work defines a novel route for exploiting naturally occurring plant microarchitectures to support the repair of functional spinal cord tissue.

2019 ◽  
Vol 49 (6) ◽  
pp. 673-682
Author(s):  
JiaYin LI ◽  
SuFang HAN ◽  
ZhiFeng XIAO ◽  
JianWu DAI

2021 ◽  
Vol 13 ◽  
Author(s):  
Junhao Liu ◽  
Ruoyao Li ◽  
Zucheng Huang ◽  
Junyu Lin ◽  
Wei Ji ◽  
...  

Protecting white matter is one of the key treatment strategies for spinal cord injury (SCI), including alleviation of myelin loss and promotion of remyelination. Rapamycin has been shown neuroprotective effects against SCI and cardiotoxic effects while enhancing autophagy. However, specific neuroprotection of rapamycin for the white matter after cervical SCI has not been reported. Therefore, we aim to evaluate the role of rapamycin in neuroprotection after hemi-contusion SCI in mice. Forty-six 8-week-old mice were randomly assigned into the rapamycin group (n = 16), vehicle group (n = 16), and sham group (n = 10). All mice of the rapamycin and vehicle groups received a unilateral contusion with 1.2-mm displacement at C5 followed by daily intraperitoneal injection of rapamycin or dimethyl sulfoxide solution (1.5 mg⋅kg–1⋅day–1). The behavioral assessment was conducted before the injury, 3 days and every 2 weeks post-injury (WPI). The autophagy-related proteins, the area of spared white matter, the number of oligodendrocytes (OLs) and axons were evaluated at 12 WPI, as well as the glial scar and the myelin sheaths formed by Schwann cells at the epicenter. The 1.2 mm contusion led to a consistent moderate–severe SCI in terms of motor function and tissue damage. Rapamycin administration promoted autophagy in spinal cord tissue after injury and reduced the glial scar at the epicenter. Additionally, rapamycin increased the number of OLs and improved motor function significantly than in the vehicle group. Furthermore, the rapamycin injection resulted in an increase of Schwann cell-mediated remyelination and weight loss. Our results suggest that rapamycin can enhance autophagy, promote Schwann cell myelination and motor function recovery by preserved neural tissue, and reduce glial scar after hemi-contusive cervical SCI, indicating a potential strategy for SCI treatment.


2021 ◽  
Author(s):  
Mingkun Yang ◽  
Xiaoqian Dang ◽  
Xu Zhang ◽  
Chuan Liu ◽  
Min He

Abstract BackgroundTo investigate the effect of mmu-miR-27a-5p on macrophage polarization in the injured spinal cord and the recovery of motor function after spinal cord injury (SCI) in mice.MethodsA total of 160 specific-pathogen-free male mice were randomly divided into sham, model, mmu-miR-27a-5p, mmu-miR-27a-5p-negative control (NC) groups, with 40 mice in each group. Hindlimb motor function was assessed using the Basso Mouse scale (BMS) before injury and at 1, 3, 7, and 14 days after surgery. Spinal cord tissue samples were obtained at 1, 3, 7, and 14 days after surgery, and macrophage polarization types were detected by using western blot analysis, immunofluorescence, flow cytometry and RT-qPCR.ResultsThe BMS score in the mmu-miR-27a-5p group was significantly higher than that in the model and mmu-miR-27a-5p-NC groups at 7 and 14 days after SCI (X2=26.45-57.62, P<0.05). No significant changes in the expression of M1 markers IL-1β, TNF-α and M2 markers IL-10, Arginase-1 at each time point in the sham group (P=0.96). The expression of IL-1β and TNF-α was significantly lower, while the expression of IL-10 and Arginase-1 were significantly higher in the mmu-miR-27a-5p group as compared to the model and mmu-miR-27a-5p-NC groups at 7 and 14 days after SCI (P<0.05).ConclusionAdministration of mmu-miR-27a-5p can promote the polarization of macrophages to the M2 phenotype in the injured spinal cord, and improve motor function recovery within 14 days after SCI in mice.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuyo Maeda ◽  
Takashi Otsuka ◽  
Masaaki Takeda ◽  
Takahito Okazaki ◽  
Kiyoharu Shimizu ◽  
...  

AbstractCell-based therapy using mesenchymal stem cells (MSCs) is a novel treatment strategy for spinal cord injury (SCI). MSCs can be isolated from various tissues, and their characteristics vary based on the source. However, reports demonstrating the effect of transplanted rat cranial bone-derived MSCs (rcMSCs) on rat SCI models are lacking. In this study, we determined the effect of transplanting rcMSCs in rat SCI models. MSCs were established from collected bone marrow and cranial bones. SCI rats were established using the weight-drop method and transplanted intravenously with MSCs at 24 h post SCI. The recovery of motor function and hindlimb electrophysiology was evaluated 4 weeks post transplantation. Electrophysiological recovery was evaluated by recording the transcranial electrical stimulation motor-evoked potentials. Tissue repair after SCI was assessed by calculating the cavity ratio. The expression of genes involved in the inflammatory response and cell death in the spinal cord tissue was assessed by real-time polymerase chain reaction. The transplantation of rcMSCs improved motor function and electrophysiology recovery, and reduced cavity ratio. The expression of proinflammatory cytokines was suppressed in the spinal cord tissues of the rats that received rcMSCs. These results demonstrate the efficacy of rcMSCs as cell-based therapy for SCI.


2019 ◽  
Vol 44 (2) ◽  
pp. 498-506 ◽  
Author(s):  
Belen G. Alvarado-Sanchez ◽  
Hermelinda Salgado-Ceballos ◽  
Sergio Torres-Castillo ◽  
Juan Rodriguez-Silverio ◽  
Monica E. Lopez-Hernandez ◽  
...  

2021 ◽  
Vol 14 ◽  
Author(s):  
Yin Hongna ◽  
Tian Hongzhao ◽  
Li Quan ◽  
Feng Delin ◽  
Liu Guijun ◽  
...  

Jia-Ji electro-acupuncture (EA) has been widely applied in clinic to exhibit curative effects on spinal cord injury (SCI). However, its underlying mechanisms leading to improvement of motor function after SCI remain unclear. Allen’s method was made by NYU Impactor M-III equipment to create the SCI rats model. Rats were randomly divided into four groups: Sham (only laminectomy), Model (SCI group), EA (SCI + Jia-Ji EA treatment), EA + CQ (SCI + Jia-Ji EA treatment + inhibitor chloroquine). Basso-Beattie-Bresnahan assessment showed improvement of hind limb motor function after Jia-Ji electro-acupuncture treatment. Histological change of injured spinal cord tissue was alleviated after treatment, observed by hematoxylin-eosin and Nissl staining. The mRNA and protein expression levels of RIPK1, RIPK3 and MLKL were decreased in EA group. Besides, the increased expression of LC3 and reduced expression of P62 after treatment compared with Model group, confirmed that Jia-Ji electro-acupuncture could enhance the autophagy flux. Electron microscopy imaging showed increasing the number of lysosomes, autophagosomes, and autolysosomes after Jia-Ji electro-acupuncture treatment. Furthermore, inhibition of lysosome function with CQ led to partly eliminate the effect of EA on reducing necroptosis. These data make the case that Jia-Ji electro-acupuncture treatment may improve locomotor function by promoting autophagy flux and inhibiting necroptosis.


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