Repair, protection and regeneration of spinal cord injury

Cao, Xiaojian; Feng, Shiqing; Fu, Changfeng; Gao, Kai; Guo, Jiasong; Guo, Xiaodong; He, Xijing; Huang, Ziwei; Li, Zhonghai; Liu, Ling; Liu, Rong-han; Lü, He‐Zuo; Mei, Xifan; Ning, Bin; Ning, Guangzhi; Qian, Changhui; Qin, Jie; Qu, Yanzhen; Saijilafu,; Shi, Bo; Sui, Tao; Sun, Tiansheng; Wang, Jian; Wen, Jingkun; Xiao, Jian; Xu, Bin; Xu, Haidong; Yu, Panpan; Zhi-cheng, Zhang; Zhou, Yong; Zhou, Yulong

doi:10.4103/1673-5374.172314

Cited by 24 publications

(11 citation statements)

References 104 publications

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“…This pathway has also been shown to play an important role in the pathophysiology of SCI [6,4,7]. For example, upregulation of RhoA was observed after SCI [8].…”

Section: Introductionmentioning

confidence: 92%

RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation

Walker

et al. 2016

Mol Neurobiol

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Activation of RhoA/Rho kinase leads to growth cone collapse and neurite retraction. Although RhoA/Rho kinase inhibition has been shown to improve axon regeneration, remyelination and functional recovery, its role in neuronal cell death remains unclear. To determine whether RhoA/Rho kinase played a role in neuronal death after injury, we investigated the relationship between RhoA/Rho kinase and cytosolic phospholipase A 2 (cPLA 2 ), a lipase that mediates inflammation and cell death, using an in vitro neuronal death model and an in vivo contusive spinal cord injury model performed at the 10 th thoracic (T10) vertebral level. We found that coadministration of TNF-α and glutamate induced spinal neuron death, and activation of RhoA, Rho kinase and cPLA 2 . Inhibition of RhoA, Rho kinase and cPLA 2 significantly reduced TNF-α/glutamate-induced cell death by 33%, 52% and 43%, respectively (p < 0.001). Inhibition of RhoA and Rho kinase also significantly down-regulated cPLA 2 activation by 66% and 60%, respectively (p < 0.01). Furthermore, inhibition of RhoA and Rho kinase reduced the release of arachidonic acid, a downstream substrate of cPLA 2 . The immunofluorescence staining showed that ROCK 1 or ROCK 2, two isoforms of Rho kinase, was co-localized with cPLA 2 in neuronal cytoplasm. Interestingly, co-immunoprecipitation (Co-IP) assay showed that ROCK 1 or ROCK 2 , bonded directly with cPLA 2 and phospho-cPLA 2 . When the Rho kinase inhibitor Y27632 was applied in mice with T10 contusion injury, it significantly decreased cPLA 2 activation and expression, and reduced injury-induced apoptosis in the lesion area. Taken together, our results reveal a novel mechanism of RhoA/Rho kinase-mediated neuronal death through regulating cPLA 2 activation.

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“…This pathway has also been shown to play an important role in the pathophysiology of SCI [6,4,7]. For example, upregulation of RhoA was observed after SCI [8].…”

Section: Introductionmentioning

confidence: 92%

RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation

Walker

et al. 2016

Mol Neurobiol

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“…When collagen degrades, the fibrous ring ruptures and the protrusion of the nucleus pulposus can press on a nerve root and/or the spinal cord, bursting the nucleus of the disc and damaging the nerve and compressing the spinal cord. Interestingly, unlike altered proteins related to spinal cord injury (transferrin–TF, matrix metalloproteinases–MMPs, insulin-like growth factor 1–IGF-1 and apolipoprotein E–APO E) [ 54 , 55 ], no metabolites reported in both untargeted and targeted metabolomics SCI-related studies [ 56 ] were found to be altered. This might be explained by the severity of SCI itself in the IVDH group, which was mild.…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Approach to Elucidate Cerebrospinal Fluid Changes in Dogs with Intervertebral Disc Herniation

Horvatić

Gelemanović

Pirkić

et al. 2021

IJMS

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Herniation of the intervertebral disc (IVDH) is the most common cause of neurological and intervertebral disc degeneration-related diseases. Since the disc starts to degenerate before it can be observed by currently available diagnostic methods, there is an urgent need for novel diagnostic approaches. To identify molecular networks and pathways which may play important roles in intervertebral disc herniation, as well as to reveal the potential features which could be useful for monitoring disease progression and prognosis, multi-omics profiling, including high-resolution liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and tandem mass tag (TMT)-based proteomics was performed. Cerebrospinal fluid of nine dogs with IVDH and six healthy controls were used for the analyses, and an additional five IVDH samples were used for proteomic data validation. Furthermore, multi-omics data were integrated to decipher a complex interaction between individual omics layers, leading to an improved prediction model. Together with metabolic pathways related to amino acids and lipid metabolism and coagulation cascades, our integromics prediction model identified the key features in IVDH, namely the proteins follistatin Like 1 (FSTL1), secretogranin V (SCG5), nucleobindin 1 (NUCB1), calcitonin re-ceptor-stimulating peptide 2 precursor (CRSP2) and the metabolites N-acetyl-D-glucosamine and adenine, involved in neuropathic pain, myelination, and neurotransmission and inflammatory response, respectively. Their clinical application is to be further investigated. The utilization of a novel integrative interdisciplinary approach may provide new opportunities to apply innovative diagnostic and monitoring methods as well as improve treatment strategies and personalized care for patients with degenerative spinal disorders.

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“…Another important therapeutic target that is implicated in scar formation and functional recovery is miR-21, which appears to be involved in the regulation of the transforming growth factor-β (TGF-β)/Small mother against decapentaplegic (SMAD) signaling pathway, and the PTEN/PI3K/AKT signaling pathway [ 18 , 107 ]. In a study that was performed by Xie et al, the therapeutic effect of miR-21 was investigated in a model of acute thoracic SCI.…”

Section: Mirnas For Neuronal Regeneration In Scimentioning

confidence: 99%

MiRNAs as Promising Translational Strategies for Neuronal Repair and Regeneration in Spinal Cord Injury

Silvestro

Mazzon

2022

Cells

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Spinal cord injury (SCI) represents a devastating injury to the central nervous system (CNS) that is responsible for impaired mobility and sensory function in SCI patients. The hallmarks of SCI include neuroinflammation, axonal degeneration, neuronal loss, and reactive gliosis. Current strategies, including stem cell transplantation, have not led to successful clinical therapy. MiRNAs are crucial for the differentiation of neural cell types during CNS development, as well as for pathological processes after neural injury including SCI. This makes them ideal candidates for therapy in this condition. Indeed, several studies have demonstrated the involvement of miRNAs that are expressed differently in CNS injury. In this context, the purpose of the review is to provide an overview of the pre-clinical evidence evaluating the use of miRNA therapy in SCI. Specifically, we have focused our attention on miRNAs that are widely associated with neuronal and axon regeneration. “MiRNA replacement therapy” aims to transfer miRNAs to diseased cells and improve targeting efficacy in the cells, and this new therapeutic tool could provide a promising technique to promote SCI repair and reduce functional deficits.

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Repair, protection and regeneration of spinal cord injury

Cited by 24 publications

References 104 publications

RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation

RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation

Multi-Omics Approach to Elucidate Cerebrospinal Fluid Changes in Dogs with Intervertebral Disc Herniation

MiRNAs as Promising Translational Strategies for Neuronal Repair and Regeneration in Spinal Cord Injury

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