4.6 Review

Microglial voltage-gated proton channel Hv1 in spinal cord injury

期刊

NEURAL REGENERATION RESEARCH
卷 17, 期 6, 页码 1183-+

出版社

WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.327325

关键词

Hv1 proton channel; ion channels; microglia; NADPH oxidase; pH regulation; reactive oxygen species; spinal cord injury

资金

  1. National Institutes of Health [R01NS110949, R01NS088627, R01NS112144, R01NS110825, R21AG064159]

向作者/读者索取更多资源

Microglia play a crucial role in spinal cord injury, but excessive activation can cause secondary damage. The voltage-gated proton channel Hv1 is found to regulate microglial activation and its deficiency can alleviate secondary damage and improve neuronal recovery.
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.

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