Contribution of Spinal Cord Oligodendrocytes to Neuroinflammatory Diseases and Pain

2019 ◽  
Vol 26 (31) ◽  
pp. 5781-5810 ◽  
Author(s):  
Sergio M. Borghi ◽  
Victor Fattori ◽  
Miriam S.N. Hohmann ◽  
Waldiceu A. Verri
Keyword(s):  
Spinal Cord ◽  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Traumatic Injury ◽  
Biological Properties ◽  
Original Research ◽  
High Morbidity ◽  
Pain Processing ◽  
Cns Inflammation ◽  
Beneficial Effects

Background: Neuroinflammatory diseases that affect spinal cord or associated spinal nerves represent challenging conditions for management in current medicine because of their complex pathology, poor prognosis, and high morbidity, which strikingly reduces the quality of life of patients. In this sense, a better understanding of the cellular and molecular mechanisms of spinal cord neuroinflammation might contribute to the development of novel therapies. Oligodendrocytes have unique and vital biological properties in central nervous system (CNS) homeostasis and physiology. A growing body of experimental evidence demonstrates that these glial cells are involved in the pathophysiological mechanisms underlying many chronic, neurodegenerative, and incapacitating CNS disorders. These cells also have important implications for the development and maintenance of neural plasticity and chronic pain states. On the other hand, evidence indicates that oligodendrocytes and their products may act in favor of CNS promoting beneficial effects orchestrating CNS tissue repair after injury. Objective: The present review aims to explore the multi-faceted actions of spinal cord oligodendrocyte progenitors cells (OPCs) and mature oligodendrocytes in CNS inflammation and pathology, addressing their roles in experimental and clinical settings. A major focus was given to spinal cord amyotrophic lateral sclerosis, multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE), traumatic injury and pain processing. Methods: This review analyses and discusses published original research articles regarding the role of OPCs/oligodendrocytes in spinal cord inflammation and pain processing. Results and Conclusion: Findings from a number of clinical and experimental paradigms suggest spinal cord OPCs/oligodendrocytes are a potential therapeutic target for the control of neuroinflammation.

scholarly journals A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2245
Author(s):  
Jue-Zong Yeh ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Yi-Wen Wang ◽  
Gang-Yi Fan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Neural Plasticity ◽  
Collagen Scaffold ◽  
Glial Scar ◽  
Beneficial Effects ◽  
Cord Injury

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.

scholarly journals Biogenesis, functions and clinical significance of circRNAs in gastric cancer

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Chan Shan ◽  
Yinfeng Zhang ◽  
Xiaodan Hao ◽  
Jinning Gao ◽  
Xinzhe Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Disease Diagnosis ◽  
Biological Properties ◽  
Circular Rnas ◽  
High Morbidity ◽  
Malignant Tumours ◽  
Diagnosis And Prognosis ◽  
Covalently Linked ◽  
New Biomarkers

Abstract Gastric cancer (GC) is one of the most common malignant tumours in the world and has high morbidity and mortality. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently linked circular structures. In recent years, plentiful circRNAs have been discovered that participate in many biological processes, including the initiation and development of tumours. Increasing evidences suggest important biological functions of circRNAs, implying that circRNAs may serve as vital new biomarkers and targets for disease diagnosis and prognosis. Among these, circRNAs are tend to aberrantly expressed and are regarded as potential biomarkers in the carcinogenesis and progression of GC. This review systematically summarised the biogenesis, biological properties and functions of circRNAs, with a focus on their relationship with GC, as well as their probable clinical implications on GC. As our cognition of the relation between circRNAs and GC deepens, more molecular mechanisms of GC progression will be discovered, and new therapeutic strategies will be used for the prevention and treatment of GC.

Electrical epidural stimulation of the cervical spinal cord: Implications for spinal respiratory neuroplasticity after spinal cord injury

2021 ◽  
Author(s):  
Ian G Malone ◽  
Rachel L Nosacka ◽  
Marissa A Nash ◽  
Kevin J Otto ◽  
Erica A Dale
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Cervical Spinal Cord ◽  
Motor Nucleus ◽  
Epidural Stimulation ◽  
Locomotor Function ◽  
Lumbosacral Spinal Cord ◽  
Cord Injury

Traumatic cervical spinal cord injury (cSCI) can lead to damage of bulbospinal pathways to the respiratory motor nuclei and consequent life-threatening respiratory insufficiency due to respiratory muscle paralysis/paresis. Reports of electrical epidural stimulation (EES) of the lumbosacral spinal cord to enable locomotor function after SCI are encouraging, with some evidence of facilitating neural plasticity. Here, we detail the development and success of EES in recovering locomotor function with consideration of stimulation parameters and safety measures to develop effective EES protocols. EES is just beginning to be applied in other motor, sensory, and autonomic systems; however, there has only been moderate success in preclinical studies aimed at improving breathing function after cSCI. Thus, we explore rationale for applying EES to the cervical spinal cord, targeting the phrenic motor nucleus for the restoration of breathing. We also suggest cellular/molecular mechanisms by which EES may induce respiratory plasticity including a brief examination of sex-related differences in these mechanisms. Finally, we suggest more attention be paid to the effects of specific electrical parameters that have been used in the development of EES protocols and how that can impact the safety and efficacy for those receiving this therapy. Ultimately, we aim to inform readers about the potential benefits of EES in the phrenic motor system and encourage future studies in this area.

scholarly journals New insights into glial scar formation after spinal cord injury

2021 ◽  
Author(s):  
Amanda Phuong Tran ◽  
Philippa Mary Warren ◽  
Jerry Silver
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Molecular Mechanisms ◽  
Complex Structure ◽  
Traumatic Injury ◽  
Treatment Strategies ◽  
The Body ◽  
Cns Injury ◽  
Loss Of Function ◽  
Cord Injury

AbstractSevere spinal cord injury causes permanent loss of function and sensation throughout the body. The trauma causes a multifaceted torrent of pathophysiological processes which ultimately act to form a complex structure, permanently remodeling the cellular architecture and extracellular matrix. This structure is traditionally termed the glial/fibrotic scar. Similar cellular formations occur following stroke, infection, and neurodegenerative diseases of the central nervous system (CNS) signifying their fundamental importance to preservation of function. It is increasingly recognized that the scar performs multiple roles affecting recovery following traumatic injury. Innovative research into the properties of this structure is imperative to the development of treatment strategies to recover motor function and sensation following CNS trauma. In this review, we summarize how the regeneration potential of the CNS alters across phyla and age through formation of scar-like structures. We describe how new insights from next-generation sequencing technologies have yielded a more complex portrait of the molecular mechanisms governing the astrocyte, microglial, and neuronal responses to injury and development, especially of the glial component of the scar. Finally, we discuss possible combinatorial therapeutic approaches centering on scar modulation to restore function after severe CNS injury.

scholarly journals Beneficial Effects of Electroacupuncture on Neuropathic Pain Evoked by Spinal Cord Injury and Involvement of PI3K-mTOR Mechanisms

2018 ◽  
Vol 21 (1) ◽  
pp. 5-13 ◽  
Author(s):  
Yujie Wang ◽  
Yu Zhao ◽  
Xiaohui Ma ◽  
Jing Li ◽  
Junling Hou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Molecular Mechanisms ◽  
Mtor Signaling ◽  
Superficial Dorsal Horn ◽  
Beneficial Effects ◽  
Thermal Pain ◽  
Cord Injury

The purpose of this study was to examine the beneficial effects of electroacupuncture (EA) on neuropathic pain evoked by spinal cord injury (SCI) and determine the underlying molecular mechanisms of these effects. SCI was induced in rats. Behavioral tests were performed to examine pain responses induced by mechanical and thermal stimulation. Western blot analysis was used to measure the protein expression of phosphorylated mammalian target of rapamycin (p-mTOR), mTOR-mediated phosphorylated ribosomal protein S6 kinase beta-1 (p-S6K1), and phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p-4E-BP1) in the superficial dorsal horn of the spinal cord. We showed that SCI increased the expression of p-mTOR, p-S6K1, and p-4E-BP1. The EA intervention attenuated the upregulation of mTOR signaling and alleviated mechanical and thermal pain responses in SCI rats. Blocking spinal mTOR by intrathecal injection of rapamycin also inhibited mechanical and thermal pain. In addition, blocking spinal phosphorylated phosphatidylinositide 3-kinase (p-PI3K) pathway attenuated p-mTOR pathways and mechanical and thermal hyperalgesia in SCI rats. EA also decreased the enhanced p-PI3K in the superficial dorsal horn of SCI rats. In conclusion, findings revealed specific signaling pathways that lead to neuropathic pain in response to SCI, including activation of PI3K-mTOR signaling. Further, results link the beneficial role of EA in alleviating SCI-induced neuropathic pain to its effect on these molecular mechanisms.

scholarly journals Hydroxytyrosol Inhibits Protein Oligomerization and Amyloid Aggregation in Human Insulin

2020 ◽  
Vol 21 (13) ◽  
pp. 4636
Author(s):  
Ivana Sirangelo ◽  
Margherita Borriello ◽  
Silvia Vilasi ◽  
Clara Iannuzzi
Keyword(s):  
Olive Oil ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Neuroblastoma Cell ◽  
Biological Properties ◽  
Protein Oligomerization ◽  
Amyloid Aggregation ◽  
Beneficial Effects ◽  
Phenolic Components ◽  
Biophysical Approach

Hydroxytyrosol (HT), one of the main phenolic components of olive oil, has attracted considerable interest for its biological properties, including a remarkable antioxidant and anti-inflammatory power and, recently, for its ability to interfere with the amyloid aggregation underlying several human diseases. We report here a broad biophysical approach and cell biology techniques that allowed us to characterize the molecular mechanisms by which HT affects insulin amyloid aggregation and the related cytotoxicity. Our data show that HT is able to fully inhibit insulin amyloid aggregation and this property seems to be ascribed to the stabilization of the insulin monomeric state. Moreover, HT completely reverses the toxic effect produced by amyloid insulin aggregates in neuroblastoma cell lines by fully inhibiting the production of toxic amyloid species. These findings suggest that the beneficial effects of olive oil polyphenols, including HT, may arise from multifunctional activities and suggest possible a application of this natural compound in the prevention or treatment of amyloid-associated diseases.

Delayed Treatment of Spinal Cord Injury In Young: A Case Report

2018 ◽  
Vol 1 (2) ◽  
pp. 15
Author(s):  
Joshua Sutikno
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Traffic Accidents ◽  
Epidemiological Data ◽  
Morbidity Rate ◽  
High Morbidity ◽  
Low Back ◽  
Traditional Treatment ◽  
Delayed Treatment ◽  
Cord Injury

Background: Spinal cord injury (SCI), one of the problems caused by traffic accidents, has a high morbidity in developing country like Indonesia. In Indonesia, the use of motorcycles is increasing every year. The epidemiological data from Fatmawati Hospital of spinal cord injury in 2014 was 104 cases both traumatic and non-traumatic SCI. In this case, a young boy with worsening of SCI, delayed the treatment for about 3 months.Case: A 19 years-old male complained of limbs paralysis for the past two weeks. He felt numbness and tingling in hamstring and calf areas. From past medical history, he had a motorcycle accident 3 months prior. After the accident, he suffered from extreme low back pain, but he could still move his legs. Due to economic restrictions, the patient refused to go to the hospital, and they chose a traditional treatment. For about three months, the pain was decreasing, but he was never pain-free. As the symptoms continued to worsen, the neurosurgeon decided to decompress the spinal cord and performed discectomy. After a week of treatment, the pain disappeared, motor muscle got better, and he could feel again the sensation on the dermatome of S1. Conclusion: Early treatment is recommended to get a better outcome. The surgery is not the only treatment, rehabilitation and orthotics using are important too. Delayed treatment increases morbidity rate.

Excitotoxicity as a Target Against Neurodegenerative Processes

2020 ◽  
Vol 26 (12) ◽  
pp. 1251-1262 ◽  
Author(s):  
Octavio Binvignat ◽  
Jordi Olloquequi
Keyword(s):  
Neurodegenerative Diseases ◽  
Effective Treatment ◽  
Molecular Mechanisms ◽  
Prolonged Exposure ◽  
Mitochondrial Dysfunctions ◽  
Beneficial Effects ◽  
Clinical Investigations ◽  
Turn Over ◽  
Excitotoxic Cell Death ◽  
Lateral Sclerosis

: The global burden of neurodegenerative diseases is alarmingly increasing in parallel to the aging of population. Although the molecular mechanisms leading to neurodegeneration are not completely understood, excitotoxicity, defined as the injury and death of neurons due to excessive or prolonged exposure to excitatory amino acids, has been shown to play a pivotal role. The increased release and/or decreased uptake of glutamate results in dysregulation of neuronal calcium homeostasis, leading to oxidative stress, mitochondrial dysfunctions, disturbances in protein turn-over and neuroinflammation. : Despite the anti-excitotoxic drug memantine has shown modest beneficial effects in some patients with dementia, to date, there is no effective treatment capable of halting or curing neurodegenerative diseases such as Alzheimer’s disease, Parkinson disease, Huntington’s disease or amyotrophic lateral sclerosis. This has led to a growing body of research focusing on understanding the mechanisms associated with the excitotoxic insult and on uncovering potential therapeutic strategies targeting these mechanisms. : In the present review, we examine the molecular mechanisms related to excitotoxic cell death. Moreover, we provide a comprehensive and updated state of the art of preclinical and clinical investigations targeting excitotoxic- related mechanisms in order to provide an effective treatment against neurodegeneration.

Diosgenin: Therapeutic Action, Pharmacology and Applications

2017 ◽  
Vol 5 (1) ◽  
pp. 7-15
Author(s):  
Sanasam Sanjeev ◽  
◽  
Maibam Sunita Devi ◽  
Khushboo Maurya ◽  
Vikas Kumar Roy ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Drug Development ◽  
Liver Diseases ◽  
Potential Role ◽  
Wide Spectrum ◽  
Herbal Product ◽  
Biological Properties ◽  
Therapeutic Action ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Beneficial Effects

Diosgenin [25R-spriost-5-en-3þ-ol], is an important steroidal metabolite found in various plant species. The discovery of diosgenin has made it one of the most researched and studied herbal product. Moreover, there is excellent opportunity to address whether diosgenin plays a role in chemoprevention versus therapy, or both. However, rigorous experimental based evidence in support of ethnomedicine-derived notions would lead to the development of products relevant to drug development. The health beneficial effects of diosgenin are further extended to its potential role to treat other ailments such as HIV and hepatitis-C infections as well as liver diseases. There is little information regarding the bioavailability, pharmacokinetics and pharmacodynamics of diosgenin in relation to its health beneficial effects. It has been reported to have wide spectrum of biological properties that contributes to several diseases in its role as a health beneficial phytochemical by citing new studies.

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