Voltage-gated proton channel contributes to secondary damage following spinal cord injury

Traumatic injury to the spinal cord initiates a series of destructive cellular processes that exacerbate tissue damage at and beyond the original site of injury. These processes include oxidative stress responses and pro-inflammatory cascades that can lead to neuronal loss and demyelination of surviving axons. Previous work in our lab has shown that the voltage-gated proton channel Hv1 is necessary for NADPH oxidase-dependent reactive oxygen species (ROS) production by microglia. This means that Hv1 mediated microglial ROS could be a mechanism to cause neuronal damage under disease conditions. Therefore, we hypothesize that Hv1 contributes to ROS production in microglia after SCI, and loss of function can alleviate secondary injury. To test this, we utilized a moderate spinal cord contusive injury model with adult wild-type and Hv1-/- mice, with the aim of studying the role of Hv1 in microglia activation, ROS production, pro-inflammatory response, neuronal cell death, and demyelination. Our results showed that loss of Hv1 reduced microglial activation following spinal cord injury. Moreover, loss of Hv1 alleviated some of the oxidative stress-mediated secondary injury, as well as inflammatory response. Hv1-/- mice exhibited increased neuronal survival, white matter sparing, and improved locomotive recovery following spinal cord injury. Together, the current study suggested that after spinal cord injury, Hv1 is a potential treatment target to reduce secondary injury.M.S.Includes bibliographical referencesby Jiaying Zhen