Proton-Activated Chloride Channel Modulates Motor Function after Acute Spinal Cord Injury

Spinal cord injury (SCI) disrupts motor, sensory, and autonomic functions, profoundly impairing quality of life. Here, we investigate the role of the proton-activated chloride (PAC) channel, encoded by Pacc1, in motor function recovery following SCI. We found that PAC is expressed in the spinal cord, predominantly in microglia, and its expression markedly increases after injury. In Pacc1 knockout mice, motor recovery was significantly improved, accompanied by reduced microgliosis. Moreover, microglia-specific deletion of Pacc1 decreased lesion volume and further enhanced motor recovery, as demonstrated by behavioral assessments. Mechanistically, loss of Pacc1 in microglia suppressed excessive microglial activation and the release of pro-inflammatory cytokines after injury. Together, these findings identify the PAC channel as an injury-induced regulator that aggravates inflammation and impairs motor recovery. Targeting PAC may thus represent a promising therapeutic strategy to mitigate inflammation and promote spinal cord repair after SCI.