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Updated: Oct 13, 2025
Identifying Microglia and Peripheral Infiltrating Macrophages in the Injured Spinal Cords Using Flow Cytometry
Published on: June 24, 2025
Microglial voltage-gated proton channel Hv1 in spinal cord injury
Jiaying Zheng1, Madhuvika Murugan2, Lingxiao Wang1
1Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Abstract:
After spinal cord injury, microglia as the first responders to the lesion display both beneficial and detrimental characteristics. Activated microglia phagocyte and eliminate cell debris, release cytokines to recruit peripheral immune cells to the injury site. Excessively activated microglia can aggravate the secondary damage by producing extravagant reactive oxygen species and pro-inflammatory cytokines. Recent studies demonstrated that the voltage-gated proton channel Hv1 is selectively expressed in microglia and regulates microglial activation upon injury. In mouse models of spinal cord injury, Hv1 deficiency ameliorates microglia activation, resulting in alleviated production of reactive oxygen species and pro-inflammatory cytokines. The reduced secondary damage subsequently decreases neuronal loss and correlates with improved locomotor recovery. This review provides a brief historical perspective of advances in investigating voltage-gated proton channel Hv1 and home in on microglial Hv1. We discuss recent studies on the roles of Hv1 activation in pathophysiological activities of microglia, such as production of NOX-dependent reactive oxygen species, microglia polarization, and tissue acidosis, particularly in the context of spinal cord injury. Further, we highlight the rationale for targeting Hv1 for the treatment of spinal cord injury and related disorders.
Insights
Targeting the voltage-gated proton channel Hv1 in microglia shows promise for treating spinal cord injury. Hv1 deficiency reduces harmful microglial activation, leading to less secondary damage and better recovery.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key immune cells in the central nervous system, acting as first responders to spinal cord injury (SCI).
- While initially beneficial, excessive microglial activation exacerbates secondary damage through reactive oxygen species (ROS) and pro-inflammatory cytokines.
- The voltage-gated proton channel Hv1 is selectively expressed in microglia and influences their activation state.
Purpose of the Study:
- To review the role of microglial Hv1 in SCI pathophysiology.
- To discuss the impact of Hv1 on microglial activation, ROS production, and tissue acidosis.
- To highlight Hv1 as a therapeutic target for SCI treatment.
Main Methods:
- Review of existing literature on Hv1 and microglial function in SCI models.
- Analysis of studies investigating Hv1 deficiency effects on microglial activation and SCI outcomes.
- Discussion of Hv1's role in NOX-dependent ROS production and microglia polarization.
Main Results:
- Hv1 deficiency in mice ameliorates microglial activation post-SCI.
- Reduced Hv1 activity leads to decreased ROS and pro-inflammatory cytokine production.
- Hv1 inhibition correlates with reduced neuronal loss and improved locomotor function after SCI.
Conclusions:
- Microglial Hv1 plays a critical role in SCI-induced secondary damage.
- Targeting Hv1 presents a potential therapeutic strategy for SCI.
- Further research into Hv1 modulation could lead to novel treatments for SCI and related neurological disorders.
