Background: Early administration of unfractionated heparin (UFH) after TBI reduces early in vivo circulating leukocytes (LEU) in peri-injury penumbral brain tissue, enhancing cognitive recovery 2 days after injury. It remains unclear how long this effect lasts and if this is related to persistently accumulating LEU in penumbral brain tissue. We hypothesized that UFH reduces LEU brain tissue sequestration resulting in prolonged cognitive recovery. Methods: CD1 male mice underwent either TBI by controlled cortical impact (CCI) or sham craniotomy. UFH (75U/kg or 225U/kg) or vehicle was repeatedly administered after TBI. Neurologic function (Garcia Neurological Test, GNT [maximum score=18]) and body weight loss ratios were evaluated at 24-96h after TBI. Brain and lung wet-to-dry ratios, hemoglobin levels (Hb) and brain LEU sequestration (Ly6G immunohistochemistry) were evaluated 96h post-mortem. ANOVA with Bonferroni correction determined significance (p
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