Recombinant human plasma gelsolin suppresses persistent neuroinflammation and restores hippocampal neurogenesis in murine model of decompression sickness.

Loss of plasma gelsolin (pGSN), a protein that lyses actin filaments, is implicated in the pathology of inflammatory and neurodegenerative diseases. We hypothesized that because pGSN is depleted in a murine model of decompression sickness (DCS), supplementation by administration of human recombinant (rhu-) pGSN would ameliorate inflammatory events. We observed that pGSN levels were persistently decreased in mice for at least 12 days postexposure to 790 kPa of air for 2 h. This decline was associated with elevated levels of inflammatory microparticles (MPs) in the blood and cervical lymph nodes, which previously were shown to cause neuroinflammation. In addition, these mice exhibited reduced expression of synaptic proteins, impaired neurogenesis and impaired cognitive and motor functions. Rhu-pGSN ameliorated the inflammatory changes and resulted in restored synaptic protein expression, neurogenesis, and neurological function. These findings demonstrate that neuronal dysfunction in our murine model of DCS is mediated by MPs and that rhu-pGSN can ameliorate injury even when administered in a delayed fashion. A decrease in plasma gelsolin levels and the release of inflammatory microparticles (MPs) occur in response to high pressure followed by decompression, with expression of filamentous (F)-actin leading to persistent neuroinflammation and functional deficits lasting at least 12 days. The infusion of recombinant human plasma gelsolin lyses these MPs in decompressed mice, thereby alleviating particle-associated neuronal dysfunction. Rhu-gelsolin infusion may be beneficial as a prophylactic or treatment for decompression sickness.