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 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 Synergic Effect of Combined Therapy of Hyperbaric Oxygen and Adipose-derived Mesenchymal Stem Cells on Improving Neurological Function After Acute Traumatic Spinal Cord Injury in Rat

2021 ◽  
Author(s):  
Tsung-Cheng Yin ◽  
Pei-Lin Shao ◽  
Kuan-Hung Chen ◽  
Kun-Chen Lin ◽  
John Y. Chiang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Traumatic Spinal Cord Injury ◽  
Voltage Gated ◽  
Cord Injury ◽  
Group 5 ◽  
Group 2 ◽  
Group 1

Abstract Background: This study tested whether combined hyperbaric oxygen (HBO) and allogenic adipose-derived mesenchymal stem cells (ADMSCs) would be superior to either one for improving the neurological function in rat after acute traumatic spinal cord injury (TSCI) in rat. Methods and Results: Adult-male SD rats (n=40) were equally categorized into group 1 (sham-operated control), group 2 (TSCI), group 3 (TSCI + HBO for 1.5h/day for 14 consecutive days after TSCI), group 4 (TSCI + ADMSCs/1.2x106 cells by intravenous injection at 3h and days 1/2 after TSCI) and group 5 (TSCI + HBO + ADMSCs), euthanized and spinal-cord tissue was harvested by day 49 after TSCI. The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2), inflammatory-signaling (TLR-4/MyD88/IL-1ß/TNF-α/substance-p), cell-stress signaling (PI3K/p-AKT/p-mTOR) and the voltage gated sodium channel (Nav1.3/1.8/1.9) biomarkers were highest in group 2, lowest in group 1 and significantly lower in group 5 than in groups 3/4 (all p<0.0001), but they did not differ between groups 3/4. The spinal cord-damaged area, the cellular levels of inflammatory/DNA-damaged (CD68+/GFAP+/γ-H2AX+ cells), MAPK family biomarkers (p-P38/p-JNK/p-ERK1/2) and cellular expressions of voltage gated sodium channel (Nav.1.3, Nav.1.8 and Nav.1.9 in NF200+ cells) as well as the pain facilitated cellular expressions (p-P38+/peripherin+ cells, p-JNK+/peripherin+ cells, p-ERK/NF200+ cells) exhibited an identical pattern of inflammation, whereas the neurological integrity displayed an opposite pattern of inflammation among the groups (all p<0.0001). Conclusion: Combined HBO-ADMSCs therapy offered additional benefits for protecting the neurological architectural and functional integrity against acute TSCI.

scholarly journals The voltage-gated proton channel Hv1 contributes to neuronal injury and motor deficits in a mouse model of spinal cord injury

2020 ◽  
Author(s):  
Madhuvika Murugan ◽  
Jiaying Zheng ◽  
Gongxiong Wu ◽  
Rochelle Mogilevsky ◽  
Xin Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Macrophage Activation ◽  
Neuronal Loss ◽  
Motor Recovery ◽  
Proton Channel ◽  
Motor Deficits ◽  
Voltage Gated ◽  
Secondary Damage ◽  
Cord Injury

Abstract Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated proton channel, Hv1, functionally expressed in microglia has been implicated in microglia polarization and oxidative stress in ischemic stroke. Here, we investigate whether Hv1 mediates microglial/macrophage activation and aggravates secondary damage following spinal cord injury (SCI). Following contusion SCI, wild-type (WT) mice showed significant tissue damage, white matter damage and impaired motor recovery. However, mice lacking Hv1 (Hv1-/-) showed significant white matter sparing and improved motor recovery. The improved motor recovery in Hv1-/- mice was associated with decreased interleukin-1β, reactive oxygen/ nitrogen species production and reduced neuronal loss. Further, deficiency of Hv1 directly influenced microglia activation as noted by decrease in microglia numbers, soma size and reduced outward rectifier K+ current density in Hv1-/- mice compared to WT mice at 7 d following SCI. Our results therefore implicate that Hv1 may be a promising potential therapeutic target to alleviate secondary damage following SCI caused by microglia/macrophage activation.

scholarly journals The voltage-gated proton channel Hv1 contributes to neuronal injury and motor deficits in a mouse model of spinal cord injury

2020 ◽  
Author(s):  
Madhuvika Murugan ◽  
Jiaying Zheng ◽  
Gongxiong Wu ◽  
Rochelle Mogilevsky ◽  
Xin Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Macrophage Activation ◽  
Neuronal Loss ◽  
Motor Recovery ◽  
Proton Channel ◽  
Motor Deficits ◽  
Voltage Gated ◽  
Secondary Damage ◽  
Cord Injury

Abstract Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated proton channel, Hv1, functionally expressed in microglia has been implicated in microglia polarization and oxidative stress in ischemic stroke. Here, we investigate whether Hv1 mediates microglial/macrophage activation and aggravates secondary damage following spinal cord injury (SCI). Following contusion SCI, wild-type (WT) mice showed significant tissue damage, white matter damage and impaired motor recovery. However, mice lacking Hv1 (Hv1-/-) showed significant white matter sparing and improved motor recovery. The improved motor recovery in Hv1-/- mice was associated with decreased interleukin-1β, reactive oxygen/ nitrogen species production and reduced neuronal loss. Further, deficiency of Hv1 directly influenced microglia activation as noted by decrease in microglia numbers, soma size and reduced outward rectifier K+ current density in Hv1-/- mice compared to WT mice at 7d following SCI. Our results therefore implicate that Hv1 may be a promising potential therapeutic target to alleviate secondary damage following SCI caused by microglia/macrophage activation.

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