Point of Injury Treatment with Hydrogel Containing Dexamethasone Improves Cognitive Function and Reduces Secondary Injury Response After TBI

Functional recovery after traumatic brain injury (TBI) is hindered by progressive neu-rodegeneration resulting from neuroinflammation and other secondary injury. Dexa-methasone (DX), a synthetic glucocorticoid, has been shown to reduce inflammation, but it’s systemic administration can cause a myriad of other medical issues. We aim to pro-vide a local, sustained treatment of DX for TBI. We demonstrated that PEG-bis-AA/HA-DXM hydrogels composed of polyethyleneglycol-bis-(acryloyloxy ac-etate) (PEG-bis-AA) and dexamethasone-conjugated hyaluronic acid (HA-DXM) reduced secondary injury and motor functional recovery at 7 days post injury (DPI) in a rat moderate controlled cortical impact (CCI) TBI model. In this study, we evaluated the effect of PEG-bis-AA/HA-DXM hydrogel on cognitive function and secondary injury at 14 DPI. Immediately after injury, hydrogel was placed on a injured brain and cognitive function was evaluated by Morris Water Maze test and secondary injury was evaluated by histological analysis. The hydrogel treatment groups demonstrated a decreased time to find hidden platform (target), distance to swim to target, and percent time to swim in border compared to TBI untreated rats on both training period and the probe test. We also observed reduced lesion volume and inflammatory response and apoptosis in hy-drogel treatment groups compared to the untreated TBI group.