Early Non-anticoagulant Desulfated Heparin After TBI: Reduced Brain Edema and Leukocyte Mobilization is Associated with Improved Watermaze Learning Ability Weeks After Injury

ABSTRACTBackgroundUnfractionated heparin (UFH) administered immediately after TBI reduces brain leukocyte (LEU) accumulation, and enhances early cognitive recovery, but may increase bleeding after injury. It is unknown how non-anticoagulant heparins such as 2,3-O desulfated heparin (ODSH), impact post-TBI cerebral inflammation and long term recovery. We hypothesized that ODSH after TBI reduces LEU-mediated brain inflammation and improves long term neurological recovery.MethodsCD1 male mice (n=66) underwent either TBI (controlled cortical impact; CCI) or sham craniotomy. ODSH [25mg/kg (25ODSH) or 50mg/kg (50ODSH)] or saline was administered for 48h after TBI in 46 animals. At 48h, intravital microscopy visualized rolling LEUs and fluorescent albumin leakage in the pial circulation, and the Garcia Neurological Test (GNT) assessed neurologic function. Brain edema (wet/dry ratio) was evaluated post-mortem. In a separate group of animals (n=20), learning/memory ability (% time swimming in the Probe platform quadrant) was assessed by the Morris Water Maze (MWM) 17 days after TBI. ANOVA with Bonferroni correction determined significance (p

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