scholarly journals Functions and Mechanisms of the Voltage-Gated Proton Channel Hv1 in Brain and Spinal Cord Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Junyun He ◽  
Rodney M. Ritzel ◽  
Junfang Wu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Proton Channel ◽  
Cns Injury ◽  
Loss Of Function ◽  
Cytosolic Ph ◽  
Voltage Gated ◽  
Cord Injury ◽  
Central Nervous Systems ◽  
Peripheral Immune Cells

The voltage-gated proton channel Hv1 is a newly discovered ion channel that is highly conserved among species. It is known that Hv1 is not only expressed in peripheral immune cells but also one of the major ion channels expressed in tissue-resident microglia of the central nervous systems (CNS). One key role for Hv1 is its interaction with NADPH oxidase 2 (NOX2) to regulate reactive oxygen species (ROS) and cytosolic pH. Emerging data suggest that excessive ROS production increases and requires proton currents through Hv1 in the injured CNS, and manipulations that ablate Hv1 expression or induce loss of function may provide neuroprotection in CNS injury models including stroke, traumatic brain injury, and spinal cord injury. Recent data demonstrating microglial Hv1-mediated signaling in the pathophysiology of the CNS injury further supports the idea that Hv1 channel may function as a key mechanism in posttraumatic neuroinflammation and neurodegeneration. In this review, we summarize the main findings of Hv1, including its expression pattern, cellular mechanism, role in aging, and animal models of CNS injury and disease pathology. We also discuss the potential of Hv1 as a therapeutic target for CNS injury.

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 Microglial voltage-gated proton channel Hv1 in spinal cord injury

2022 ◽  
Vol 17 (6) ◽  
pp. 1183
Author(s):  
Long-Jun Wu ◽  
Jiaying Zheng ◽  
Madhuvika Murugan ◽  
Lingxiao Wang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Proton Channel ◽  
Voltage Gated ◽  
Cord Injury

scholarly journals Knockdown of long non-coding RNA LEF1-AS1 attenuates apoptosis and inflammatory injury of microglia cells following spinal cord injury

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Sheng-Yu Cui ◽  
Wei Zhang ◽  
Zhi-Ming Cui ◽  
Hong Yi ◽  
Da-Wei Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Viability ◽  
Microglial Cells ◽  
Protective Effects ◽  
Loss Of Function ◽  
Sprague Dawley ◽  
Cord Injury ◽  
Apoptosis And Inflammation

Abstract Background Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development. Methods Using in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique. Results We revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation. Conclusion In summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.

Olfactory Mucosal Auto-transplantation in Spinal Cord Injury: A Clinical Trial, Saudi Arabia

2021 ◽  
pp. 11
Author(s):  
Ahmad Najib Ashraf ◽  
Abdulaziz Shebreen
Keyword(s):  
Clinical Trial ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Sensory Function ◽  
Cell Transplant ◽  
Loss Of Function ◽  
Neurological Improvement ◽  
Cord Injury ◽  
Distinctive Property ◽  
Independent Life

Introduction: Spinal cord injury (SCI) results in loss of nervous tissue and consequently loss of motor and sensory function. Despite significant improvements in the early medical and surgical management of SCI, there is no effective treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. Restoration of function and reversal of paralysis following SCI is among the most daunting challenges in all of neuroscience research. Methodology: We decided to study the outcomes in chronic SCI (CSCI) after autologous olfactory mucosal transplantation into the spinal cord following detethering of the cord. The human surgical procedure of autologous olfactory mucosal transplantation was first developed by Carlos Lima and his colleagues. These investigators provided guidance for the surgical procedures in this study and the procedures on the first six participants were performed in their presence. Result: Patients were screened at different centers in the kingdom. A stringent inclusion and exclusion criteria were applied. Patients for this clinical trial were selected from individuals that suffered an SCI at least 12 months before their assessment and were chronically paraplegic or tetraplegic. The final twenty participants were selected after screening more than 125 patients.  While some of them were rejected for medical reasons, some refused to participate upon receiving a full briefing and some of them were unable to fulfill the required psychosocial criteria. Conclusion: The details of the patients and the changes observed in their conditions post olfactory mucosal auto-transplantation will be discussed in detail in oral presentation with graphic results with marked significant improvement in motor and sensory levels of SCI patients as compared to before transplantation of olfactory mucosa. Olfactory unsheathing cells (OECs) are glia cells and continuous axon extension and successful topographic targeting of the olfactory receptor neurons responsible for the sense of smell (olfaction). Due to this distinctive property, OECs have been trialed in human cell transplant therapies to assist in the repair of central nervous system injuries, particularly those of the spinal cord. Although many studies have reported neurological improvement, therapy remains inconsistent and requires further improvement.

scholarly journals Treatment of spinal cord injury with mesenchymal stem cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ling Ling Liau ◽  
Qi Hao Looi ◽  
Wui Chuen Chia ◽  
Thayaalini Subramaniam ◽  
Min Hwei Ng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Poor Quality ◽  
Nerve Tissue ◽  
Current Status ◽  
Therapeutic Effects ◽  
Biological Therapies ◽  
Loss Of Function ◽  
Cord Injury

Abstract Background Spinal cord injury (SCI) is the damage to the spinal cord that can lead to temporary or permanent loss of function due to injury to the nerve. The SCI patients are often associated with poor quality of life. Results This review discusses the current status of mesenchymal stem cell (MSC) therapy for SCI, criteria to considering for the application of MSC therapy and novel biological therapies that can be applied together with MSCs to enhance its efficacy. Bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (ADSCs) have been trialed for the treatment of SCI. Application of MSCs may minimize secondary injury to the spinal cord and protect the neural elements that survived the initial mechanical insult by suppressing the inflammation. Additionally, MSCs have been shown to differentiate into neuron-like cells and stimulate neural stem cell proliferation to rebuild the damaged nerve tissue. Conclusion These characteristics are crucial for the restoration of spinal cord function upon SCI as damaged cord has limited regenerative capacity and it is also something that cannot be achieved by pharmacological and physiotherapy interventions. New biological therapies including stem cell secretome therapy, immunotherapy and scaffolds can be combined with MSC therapy to enhance its therapeutic effects.

scholarly journals Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ken Lee ◽  
Sang O Park ◽  
Pil-Cho Choi ◽  
Seung-Bum Ryoo ◽  
Haeyeong Lee ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Detrusor Overactivity ◽  
Ex Vivo ◽  
Functional Characterization ◽  
Interstitial Cells ◽  
Sk Channels ◽  
Loss Of Function ◽  
Cord Injury

AbstractVolume accommodation occurs via a novel mechanism involving interstitial cells in detrusor muscles. The interstitial cells in the bladder are PDGFRα+, and they restrain the excitability of smooth muscle at low levels and prevents the development of transient contractions (TCs). A common clinical manifestation of spinal cord injury (SCI)-induced bladder dysfunction is detrusor overactivity (DO). Although a myogenic origin of DO after SCI has been suggested, a mechanism for development of SCI-induced DO has not been determined. In this study we hypothesized that SCI-induced DO is related to loss of function in the regulatory mechanism provided by PDGFRα+ cells. Our results showed that transcriptional expression of Pdgfra and Kcnn3 was decreased after SCI. Proteins encoded by these genes also decreased after SCI, and a reduction in PDGFRα+ cell density was also documented. Loss of PDGFRα+ cells was due to apoptosis. TCs in ex vivo bladders during filling increased dramatically after SCI, and this was related to the loss of regulation provided by SK channels, as we observed decreased sensitivity to apamin. These findings show that damage to the mechanism restraining muscle contraction during bladder filling that is provided by PDGFRα+ cells is causative in the development of DO after SCI.

scholarly journals Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury

2015 ◽  
Vol 112 (43) ◽  
pp. 13360-13365 ◽  
Author(s):  
Hongmei Duan ◽  
Weihong Ge ◽  
Aifeng Zhang ◽  
Yue Xi ◽  
Zhihua Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Cns Injury ◽  
Neurotrophin 3 ◽  
Cord Injury ◽  
Transcriptome Analyses ◽  
Regeneration Capability

Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration.

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