Nerve growth factor loaded macrophage-derived nanovesicles for inhibiting neuronal apoptosis after spinal cord injury

2021 ◽  
pp. 088532822110259
Author(s):  
Nan Xia ◽  
Zhanshan Gao ◽  
Hengshuo Hu ◽  
Daoyong Li ◽  
Chuanjie Zhang ◽  
...  

Spinal cord injury (SCI) is an extremely destructive central nervous system lesion. Studies have shown that NGF can promote nerve regeneration after SCI. However, it cannot produce the desired effect due to its stability in the body and is difficulty in passing through the blood-brain barrier. In this study, we prepared nanovesicles derived from macrophage membrane encapsulating NGF (NGF-NVs) as a drug carrier for the treatment of SCI. Cell experiments showed that NGF-NVs were effectively taken up by PC12 cells and inhibited neuronal apoptosis. In vivo imaging experiments, a large quantity of NGF was delivered to the injured site with the aid of the good targeting of NVs. In animal experiments, NGF-NVs improved the survival of neurons by significantly activating the PI3K/AKT signaling pathway and had good behavioral and histological recovery effects after SCI. Therefore, NVs are a potential drug delivery vector for SCI therapy.

2017 ◽  
Vol 5 (1) ◽  
pp. 87-93
Author(s):  
O. Rybachuk ◽  
I. Arkhypchuk ◽  
Yu. Lazarenko

In recent years, there is a growing interest in the mechanisms of regeneration of damaged nerve tissue, including the spinal cord, as its injuries are quite common due to traffic accidents, industrial injuries and military actions. Damage to the spinal cord results in the loss of functional activity of the body below the injury site, which affects person’s ability to self-service and significantly reduces its efficiency. The effects of spinal injuries annually cause significant social and economic losses worldwide, including Ukraine. The development of new treatments for pathologies of the central nervous system requires mandatory pre-testing of their effectiveness in experiments in vitro and in vivo. Therefore, searching and creation of optimal animal model of spinal cord injury is in order to it meets most complete picture of the damage characteristic of real conditions in humans. This is an important task of modern neurophysiology. Such models can be used, primarily, for a more detailed clarification of the pathogenesis of all levels of nerve tissue damage and research of its own recovery potential by endogenous reparation mechanisms. In addition, experimental models allow to estimate the safety and predict the effectiveness of various therapeutic approaches to spinal cord injury.


2021 ◽  
Author(s):  
Zipeng Zhou ◽  
Dan Li ◽  
Xiangyi Fan ◽  
Yajiang Yuan ◽  
Hongyu Wang ◽  
...  

Abstract Spinal cord injury (SCI) leads to nerve cell apoptosis and loss of motor function. Herein, excessive activation of the M1 phenotype macrophages/microglia is found to be the main reason for the poor prognosis of SCI, but the selective activation phenotype (M2) macrophages/microglia facilitates the recovery of SCI. Thereafter, we used gold nanoclusters loaded berberine (BRB-AuNCs) to reduce inflammation by inhibiting the activation of M1 phenotype macrophages/microglia, which simultaneously inhibited neuronal apoptosis after SCI. In vitro and in vivo experiments showed that BRB-AuNCs reduced M1 protein marker CD86, increased M2 protein marker CD206, reduced inflammation and apoptotic cytokines (IL-1β, IL-6, TNF-α, Cleaved Caspase-3, Bax). These results indicate that BRB-AuNCs have excellent anti-inflammatory and anti-apoptotic effects by inducing the polarization of macrophages/microglia from M1 phenotype to M2 phenotype. Thereafter, the motor functions of SCI rats were significantly improved after treatment with BRB-AuNCs. This work not only provides a new way for the treatment of SCI but also broadens BRB utilization strategies.


PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e42129 ◽  
Author(s):  
Junfang Wu ◽  
Giorgi Kharebava ◽  
Chunshu Piao ◽  
Bogdan A. Stoica ◽  
Michael Dinizo ◽  
...  

Author(s):  
Dayu Pan ◽  
Shibo Zhu ◽  
Weixin Zhang ◽  
Zhijian Wei ◽  
Fuhan Yang ◽  
...  

AbstractSpinal cord injury (SCI) is catastrophic to humans and society. However, there is currently no effective treatment for SCI. Autophagy is known to serve critical roles in both the physiological and pathological processes of the body, but its facilitatory and/or deleterious effects in SCI are yet to be completely elucidated. This study aimed to use primary Schwann cell-derived exosomes (SCDEs) to treat rats after SCI. In the present study, SCDEs were purified and their efficacy in ameliorating the components of SCI was examined. Using both in vivo and in vitro experiments, it was demonstrated that SCDEs increased autophagy and decreased apoptosis after SCI, which promoted axonal protection and the recovery of motor function. Furthermore, it was discovered that an increased number of SCDEs resulted in a decreased expression level of EGFR, which subsequently inhibited the Akt/mTOR signaling pathway, which upregulated the level of autophagy to ultimately induce microtubule acetylation and polymerization. Collectively, the present study identified that SCDEs could induce axonal protection after SCI by increasing autophagy and decreasing apoptosis, and it was suggested that this may involve the EGFR/Akt/mTOR signaling pathway.


Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2245
Author(s):  
Jue-Zong Yeh ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Yi-Wen Wang ◽  
Gang-Yi Fan ◽  
...  

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.


2013 ◽  
Vol 2 (10) ◽  
pp. 731-744 ◽  
Author(s):  
Christopher J. Sontag ◽  
Hal X. Nguyen ◽  
Noriko Kamei ◽  
Nobuko Uchida ◽  
Aileen J. Anderson ◽  
...  

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