Extracellular Matrix and Oxidative Stress Following Traumatic Spinal Cord Injury: Physiological and Pathophysiological Roles and Opportunities for Therapeutic Intervention

Chio, Jonathon Chon Teng; Punjani, Nayaab; Hejrati, Nader; Zavvarian, Mohammad-Masoud; Hong, James; Fehlings, Michael G.

doi:10.1089/ars.2021.0120

Cited by 26 publications

(23 citation statements)

References 194 publications

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“…Although oxidative injury is described in osteoporotic patients [ 67 ], and as a complication of traumatic injuries to the brain and spinal cord [ 68 ], it is not the focus of fracture healing studies. Various studies have indicated the therapeutic potential of targeting oxidative stress with Gpx1 in multiple organs and diseases [ 67 , 68 , 69 , 70 ].…”

Section: Discussionmentioning

confidence: 99%

Landscape of Well-Coordinated Fracture Healing in a Mouse Model Using Molecular and Cellular Analysis

Malhan

Schmidt‐Bleek

Duda

et al. 2023

IJMS

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The success of fracture healing relies on overlapping but coordinated cellular and molecular events. Characterizing an outline of differential gene regulation throughout successful healing is essential for identifying crucial phase-specific markers and may serve as the basis for engineering these in challenging healing situations. This study analyzed the healing progression of a standard closed femoral fracture model in C57BL/6N (age = 8 weeks) wild-type male mice. The fracture callus was assessed across various days post fracture (D = days 0, 3, 7, 10, 14, 21, and 28) by microarray, with D0 serving as a control. Histological analyses were carried out on samples from D7 until D28 to support the molecular findings. Microarray analysis revealed a differential regulation of immune response, angiogenesis, ossification, extracellular matrix regulation, mitochondrial and ribosomal genes during healing. In-depth analysis showed differential regulation of mitochondrial and ribosomal genes during the initial phase of healing. Furthermore, the differential gene expression showed an essential role of Serpin Family F Member 1 over the well-known Vascular Endothelial Growth Factor in angiogenesis, especially during the inflammatory phase. The significant upregulation of matrix metalloproteinase 13 and bone sialoprotein from D3 until D21 asserts their importance in bone mineralization. The study also shows type I collagen around osteocytes located in the ossified region at the periosteal surface during the first week of healing. Histological analysis of matrix extracellular phosphoglycoprotein and extracellular signal-regulated kinase stressed their roles in bone homeostasis and the physiological bone-healing process. This study reveals previously unknown and novel candidates, that could serve as a target for specific time points in healing and to remedy cases of impaired healing.

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Section: Discussionmentioning

confidence: 99%

Landscape of Well-Coordinated Fracture Healing in a Mouse Model Using Molecular and Cellular Analysis

Malhan

Schmidt‐Bleek

Duda

et al. 2023

IJMS

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“…The extracellular matrix of the spinal cord contains structural and communication proteins involved in repair and regeneration after SCI 33,34 . They not only provide support for neuronal regeneration but also achieve homeostasis through receptor or receptor‐mediated action and the related positioning of other signal molecules in time and space, and have a positive regulatory role and signal conduction function 35 .…”

Section: Ensc Therapy On Scimentioning

confidence: 99%

Research progress of endogenous neural stem cells in spinal cord injury

Wang

Yuan

2022

Ibrain

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Spinal cord injury (SCI) is a severe disabling disease, which mainly manifests as impairments of sensory and motor functions, sexual function, bladder and intestinal functions, respiratory and cardiac functions below the injury plane.In addition, the condition has a profound effect on the mental health of patients, which often results in severe sequelae. Some patients may be paraplegic for life or even die, which places a huge burden on the family and society. There is still no effective treatment for SCI. Studies have confirmed that endogenous neural stem cells (ENSCs), as multipotent neural stem cells, which are located in the ependymal region of the central canal of the adult mammalian spinal cord, are activated after SCI and then differentiate into various nerve cells to promote endogenous repair and regeneration. However, the central canal of the spinal cord is often occluded to varying degrees in adults, and residual ependymal cells cannot be activated and do not proliferate after SCI. Besides, the destruction of the microenvironment after SCI is also an important factor that affects the proliferation and differentiation of ENSCs and spinal cord repair. Therefore, this review describes the role of ENSCs in SCI, in terms of the origin, transformation, treatment, and influencing factors, to provide new ideas for clinical treatment of SCI.

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“…When SCI occurs, the extracellular matrix is damaged and the products of membrane peroxidation are expressed. Consequently, these biomarkers can indirectly indicate damage caused by oxidative stress ( Chio et al, 2021 ), as shown in Figure 4 .…”

Section: Anti-oxidative Stressmentioning

confidence: 99%

Mechanisms of ginsenosides exert neuroprotective effects on spinal cord injury: A promising traditional Chinese medicine

Zhang

Wang

et al. 2022

Front. Neurosci.

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Spinal cord injury (SCI) is a devastating disorder of the central nervous system (CNS). It is mainly caused by trauma and reduces the quality of life of the affected individual. Ginsenosides are safe and effective traditional Chinese medicines (TCMs), and their efficacy against SCI is being increasingly researched in many countries, especially in China and Korea. This systematic review evaluated the neuroprotective effects of ginsenosides in SCI and elucidated their properties.MethodsAll experimental information and summaries used in this review were acquired from peer-reviewed articles in the relevant fields. The PubMed, Web of Science, Google Scholar, and China National Knowledge Infrastructure databases were searched for relevant articles. Information on the manual classification and selection of ginsenosides that protect against SCI is included in this review.ResultsA literature survey yielded studies reporting several properties of ginsenosides, including anti-inflammation, anti-apoptosis, anti-oxidative stress, and inhibition of glial scar formation.ConclusionIn this review, we discuss the mechanisms of action of different ginsenosides that exert neuroprotective effects in SCI. These results suggest that after further verification in the future, ginsenosides may be used as adjunctive therapy to promote neurological recovery.

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Extracellular Matrix and Oxidative Stress Following Traumatic Spinal Cord Injury: Physiological and Pathophysiological Roles and Opportunities for Therapeutic Intervention

Cited by 26 publications

References 194 publications

Landscape of Well-Coordinated Fracture Healing in a Mouse Model Using Molecular and Cellular Analysis

Landscape of Well-Coordinated Fracture Healing in a Mouse Model Using Molecular and Cellular Analysis

Research progress of endogenous neural stem cells in spinal cord injury

Mechanisms of ginsenosides exert neuroprotective effects on spinal cord injury: A promising traditional Chinese medicine

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