scholarly journals Bioengineered Zinc Oxide Nanoparticle-Loaded Hydrogel for Combinative Treatment of Spinal Cord Transection

2022 ◽  
Vol 9 ◽  
Author(s):  
Sen Lin ◽  
Hao-sen Zhao ◽  
Chang Xu ◽  
Zi-peng Zhou ◽  
Da-hao Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Zinc Oxide ◽  
Early Stage ◽  
Underlying Mechanism ◽  
Local Administration ◽  
Injured Spinal Cord ◽  
Function Recovery ◽  
Cord Injury ◽  
Gel Treatment ◽  
Systemic Application

Spinal cord injury (SCI) is one of the most destructive diseases. The neuroinflammation microenvironment needs comprehensive mitigation of damages. Thus, regulation of local, microenvironment drugs could be a potential effective treatment. However, clinical studies on SCI with common treatment have reported it to cause systemic toxicity and side effects. Zinc oxide nanoparticles (ZnONPs) have been widely reported to have satisfying anti-inflammation function. Furthermore, green synthesis procedures can improve the capability and possible utilization of ZnONPs. However, the efficient administration and underlying mechanism of ZnONPs in SCI treatment remain unclear. Herein, an innovative approach was built by utilizing ZnONPs loaded in a skeletal muscle-derived adhesive hydrogel (ZnONPs-Gel). Different from the systemic application of ZnONPs, the local administration of ZnONPs-Gel offered the ZnONPs-loaded extracellular matrix with beneficial biocompatibility to the injured spinal cord, thereby promoting effective function recovery. Mechanistically, the ZnONPs-Gel treatment not only markedly reduced ROS production but also decreased apoptosis in the injured spinal cord. Therefore, the strategy based on local administration of the ZnONPs-Gel in the early stage of SCI may be an effective therapeutic treatment.

scholarly journals EGCG modulates PKD1 and ferroptosis to promote recovery in ST rats

2020 ◽  
Vol 11 (1) ◽  
pp. 173-181 ◽  
Author(s):  
Jianjun Wang ◽  
Ying Chen ◽  
Long Chen ◽  
Yanzhi Duan ◽  
Xuejun Kuang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Functional Recovery ◽  
Antioxidant Properties ◽  
Underlying Mechanism ◽  
Maximal Effect ◽  
Loss Of Function ◽  
Protein Kinase D1 ◽  
Erk Phosphorylation ◽  
Cord Injury ◽  
Novel Strategy

AbstractBackgroundSpinal cord injury (SCI) causes devastating loss of function and neuronal death without effective treatment. (−)-Epigallocatechin-3-gallate (EGCG) has antioxidant properties and plays an essential role in the nervous system. However, the underlying mechanism by which EGCG promotes neuronal survival and functional recovery in complete spinal cord transection (ST) remains unclear.MethodsIn the present study, we established primary cerebellar granule neurons (CGNs) and a T10 ST rat model to investigate the antioxidant effects of EGCG via its modulation of protein kinase D1 (PKD1) phosphorylation and inhibition of ferroptosis.ResultsWe revealed that EGCG significantly increased the cell survival rate of CGNs and PKD1 phosphorylation levels in comparison to the vehicle control, with a maximal effect observed at 50 µM. EGCG upregulated PKD1 phosphorylation levels and inhibited ferroptosis to reduce the cell death of CGNs under oxidative stress and to promote functional recovery and ERK phosphorylation in rats following complete ST.ConclusionTogether, these results lay the foundation for EGCG as a novel strategy for the treatment of SCI related to PKD1 phosphorylation and ferroptosis.

scholarly journals The Reorganization of Insular Subregions in Individuals with Below-Level Neuropathic Pain following Incomplete Spinal Cord Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xuejing Li ◽  
Ling Wang ◽  
Qian Chen ◽  
Yongsheng Hu ◽  
Jubao Du ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Pearson Correlation ◽  
Underlying Mechanism ◽  
Anterior Insula ◽  
Incomplete Spinal Cord Injury ◽  
Cord Injury ◽  
Vas Scores ◽  
And Function

Objective. To investigate the reorganization of insular subregions in individuals suffering from neuropathic pain (NP) after incomplete spinal cord injury (ISCI) and further to disclose the underlying mechanism of NP. Method. The 3D high-resolution T1-weighted structural images and resting-state functional magnetic resonance imaging (rs-fMRI) of all individuals were obtained using a 3.0 Tesla MRI system. A comparative analysis of structure and function connectivity (FC) with insular subareas as seeds in 10 ISCI individuals with below-level NP (ISCI-P), 11 ISCI individuals without NP (ISCI-N), and 25 healthy controls (HCs) was conducted. Associations between the structural and functional alteration of insula subregions and visual analog scale (VAS) scores were analyzed using the Pearson correlation in SPSS 20. Results. Compared with ISCI-N patients, when the left posterior insula as the seed, ISCI-P showed increased FC in right cerebellum VIIb and cerebellum VIII, Brodmann 37 (BA 37). When the left ventral anterior insula as the seed, ISCI-P indicated enhanced FC in right BA18 compared with ISCI-N patients. These increased FCs positively correlated with VAS scores. Relative to HCs, ISCI-P presented increased FC in the left hippocampus when the left dorsal anterior insula was determined as the seed. There was no statistical difference in the volume of insula subregions among the three groups. Conclusion. Our study indicated that distinctive patterns of FC in each subregion of insula suggest that the insular subareas participate in the NP processing through different FC following ISCI. Further, insula subregions could serve as a therapeutic target for NP following ISCI.

scholarly journals Genistein Loaded Nanofibers Protect Spinal Cord Tissue Following Experimental Injury in Rats

2018 ◽  
Author(s):  
Mohamed Ismail ◽  
Sara Ibrahim ◽  
Azza Elamir ◽  
Amira M. Elrafei ◽  
Nageh Allam ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Spinal Cord ◽  
Drug Delivery System ◽  
Delivery System ◽  
Enhanced Recovery ◽  
Therapeutic Drug ◽  
Control Group ◽  
Spinal Cord Tissue ◽  
Injured Spinal Cord ◽  
Cord Injury

Implantable drug-delivery systems provide new means for achieving therapeutic drug concentration over a prolonged time to achieve better tissue protection and enhanced recovery. The hypothesis of the current study was to test the antioxidant and anti-inflammatory effects of genistein and nanofibers on the spinal cord tissue following experimental spinal cord injury (SCI). Rats were treated post SCI with genistein loaded on chitosan/polyvinyl alcohol (CS/PVA) nanofibers as an implantable drug-delivery system. SCI caused marked oxidative damage and inflammation as evident by the reduction in the super oxide dismutase (SOD) activity and the level of interleukin-10 (IL-10) in injured spinal cord tissue, as well as, the significant increase in the levels of nitric oxide (NO), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α). Treatment of rats post SCI with genistein and CS/PVA nanofibers improved most of the above mentioned biochemical parameters and shifted them toward the control group values. Genistein induced an increase in the activity of SOD and the level of IL-10, while causing a decrease in the levels of NO, MDA and TNF-α in injured spinal cord tissue. Genistein and CS/PVA nanofibers provide a novel combination for treating inflammatory nervous tissue conditions, especially when combined as an implantable drug-delivery system.

scholarly journals Overexpression of Rictor in the injured spinal cord promotes functional recovery in a rat model of spinal cord injury

2020 ◽  
Vol 34 (5) ◽  
pp. 6984-6998
Author(s):  
Ningning Chen ◽  
Pengxiang Zhou ◽  
Xizhe Liu ◽  
Jiachun Li ◽  
Yong Wan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Rat Model ◽  
Injured Spinal Cord ◽  
Cord Injury

scholarly journals B-RAFV600E Inhibitor Dabrafenib Attenuates RIPK3-Mediated Necroptosis and Promotes Functional Recovery after Spinal Cord Injury

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1582 ◽  
Author(s):  
Takehiro Sugaya ◽  
Haruo Kanno ◽  
Michiharu Matsuda ◽  
Kyoichi Handa ◽  
Satoshi Tateda ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Tissue Damage ◽  
Neuroprotective Effect ◽  
Neural Tissue ◽  
Injured Spinal Cord ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Cord Injury

The receptor-interacting protein kinase 3 (RIPK3) is a key regulator of necroptosis and is involved in various pathologies of human diseases. We previously reported that RIPK3 expression is upregulated in various neural cells at the lesions and necroptosis contributed to secondary neural tissue damage after spinal cord injury (SCI). Interestingly, recent studies have shown that the B-RAFV600E inhibitor dabrafenib has a function to selectively inhibit RIPK3 and prevents necroptosis in various disease models. In the present study, using a mouse model of thoracic spinal cord contusion injury, we demonstrate that dabrafenib administration in the acute phase significantly inhibites RIPK3-mediated necroptosis in the injured spinal cord. The administration of dabrafenib attenuated secondary neural tissue damage, such as demyelination, neuronal loss, and axonal damage, following SCI. Importantly, the neuroprotective effect of dabrafenib dramatically improved the recovery of locomotor and sensory functions after SCI. Furthermore, the electrophysiological assessment of the injured spinal cord objectively confirmed that the functional recovery was enhanced by dabrafenib. These findings suggest that the B-RAFV600E inhibitor dabrafenib attenuates RIPK3-mediated necroptosis to provide a neuroprotective effect and promotes functional recovery after SCI. The administration of dabrafenib may be a novel therapeutic strategy for treating patients with SCI in the future.

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