Minimizing secondary spinal cord injuries with hypertonic saline.

Spinal cord injury (SCI) disrupts white matter, causing periaxonal swelling, axonal degeneration, and impaired function. To examine vascular edema’s role, we developed a 3Dprinted dual-compartment imaging chamber to mimic and manipulate interstitial and vascular fluid dynamics in real time. We hypothesized that hypertonic saline (HTS) in the "vascular" chamber would osmotically shift fluid from the periaxonal space and preserve myelinated fibers after SCI. Using two-photon excitation microscopy, we imaged myelin and axons ex vivo in Thy1YFP+ transgenic mice following C5 contusive SCI and assessed three clinically relevant HTS concentrations versus normal saline for their effectiveness in mitigating periaxonal swelling and axonal spheroid formation. The most effective HTS concentration was then administered in vivo post-SCI to assess functional recovery in a T9 contusion model, where BMS subscores and motion sequencing (MoSeq) revealed that 3% HTS improved subtle locomotor recovery, supporting HTS as a potential therapy in secondary axonal degeneration.