Cerebral Edema and Neurological Recovery after Traumatic Brain Injury Are Worsened if Accompanied by a Concomitant Long Bone Fracture

Abstract Progression of severe traumatic brain injury (TBI) is associated with worsening cerebral inflammation, but it is unknown how a concomitant bone fracture (FX) affects this progression. Enoxaparin (ENX), a low molecular weight heparin often used for venous thromboembolic prophylaxis, decreases penumbral leukocyte (LEU) mobilization in isolated TBI and improves neurological recovery. We investigated if TBI accompanied by an FX worsens LEU-mediated cerebral inflammation and if ENX alters this process. CD1 male mice underwent controlled cortical impact (CCI) or sham craniotomy with or without an open tibial FX, and received either ENX (1 mg/kg, three times/day) or saline for 2 days following injury. Randomization defined four groups (Sham, CCI, CCI+FX, CCI+FX+ENX, n = 10/group). Two days after CCI, neurological recovery was assessed with the Garcia Neurological Test (GNT); intravital microscopy (LEU rolling and adhesion, microvascular leakage) and blood hemoglobin levels were also evaluated. Penumbral...