leptin and Brain-Injuries--Traumatic

Recent studies on insulin, leptin, osteocalcin (OCN), and bone remodeling have evoked interest in the interdependence of bone formation and energy household. Accordingly, this study attempts to investigate trauma specific hormone changes in a murine trauma model and its influence on fracture healing. Thereunto 120 female wild type (WT) and leptin-deficient mice underwent either long bone fracture (Fx), traumatic brain injury (TBI), combined trauma (Combined), or neither of it and therefore served as controls (C). Blood samples were taken weekly after trauma and analyzed for insulin and OCN concentrations. Here, WT-mice with Fx and, moreover, with combined trauma showed a greater change in posttraumatic insulin and OCN levels than mice with TBI alone. In the case of leptin-deficiency, insulin changes were still increased after bony lesion, but the posttraumatic OCN was no longer trauma specific. Four weeks after trauma, hormone levels recovered to normal/basal line level in both mouse strains. Thus, WT- and leptin-deficient mice show a trauma specific hyperinsulinaemic stress reaction leading to a reduction in OCN synthesis and release. In WT-mice, this causes a disinhibition and acceleration of fracture healing after combined trauma. In leptin-deficiency, posttraumatic OCN changes are no longer specific and fracture healing is impaired regardless of the preceding trauma.

Topics: Animals; Biomarkers; Brain Injuries, Traumatic; Disease Models, Animal; Female; Fracture Healing; Fractures, Bone; Hormones; Insulin; Leptin; Mice; Mice, Knockout; Models, Biological; Osteocalcin; Osteogenesis

The combination of traumatic brain injury (TBI) and long-bone fracture leads to increased formation of callus and mineral density in wild-type (WT) mice. However, this effect was not detected radiologically in leptin-deficient mice. Due to the complex interactions between hormonal and bone metabolism and the important role of leptin in this setting, our aim was to investigate morphologic properties and the tissue composition in the fracture callus comparing WT and leptin-deficient mice.. Female C57/Black6N mice (n=36) and leptin deficient ob/ob mice (n=36) each were assigned to two groups (fracture Fx/combined trauma Fx/TBI). Femoral osteotomy was stabilized with external fixator, TBI was induced with controlled cortical impact injury. After sacrifice of the animals, femora were harvested, cryofixated, and 7 µm slices were prepared. Staining was performed adhering to Movat's Pentachrome protocol. Histomorphometric analysis, quantifying percentage of mineralized bone area, and a semi-quantitative evaluation of bone bridging were performed.. Leptin deficient mice showed a higher rate of non-union after osteotomy, less callus formation in the osteotomy gap, and unexpected bone and cartilage formation independent of the osteotomy region.. Leptin plays an important role in fracture healing and bone formation. Without Leptin, the positive effect of TBI on fracture healing ceases. The comprehension of the underlying pathophysiological process could sign important for novel strategies in stimulation of fracture healing.

Topics: Animals; Brain Injuries, Traumatic; Disease Models, Animal; Female; Femoral Fractures; Femur; Fracture Healing; Leptin; Mice; Osteogenesis; Osteotomy

Patients with traumatic brain injury (TBI) and long-bone fractures can show increased callus formation. This effect has already been reproduced in wild-type (wt) mice. However, the mechanisms remain poorly understood. Leptin is significantly increased following TBI, while its role in bone healing remains unclear. The aim of this study was to evaluate fracture healing in leptin-deficient ob/ob mice and to measure any possible impact of TBI on callus formation. 138 female, 12 weeks old, ob/ob mice were divided into four groups: Control, fracture, TBI and combined trauma. Osteotomies were stabilized with an external fixator; TBI was induced with Controlled Cortical Impact Injury. Callus bridging was weekly evaluated with in vivo micro-CT. Biomechanical testing was performed ex vivo. Micro-CT showed high non-union rates after three and four weeks in the fracture and combined trauma group. No differences were observed in callus volume, density and biomechanical properties at any time point. This study shows that bony bridging is impaired in the present leptin-deficient trauma model. Furthermore, the phenomenon of increased callus formation after TBI could not be reproduced in ob/ob mice, as in wt mice. Our findings suggest that the increased callus formation after TBI may be dependent on leptin signaling.

Topics: Animals; Bony Callus; Brain Injuries, Traumatic; Female; Femoral Fractures; Fracture Healing; Leptin; Mice; Mice, Obese; Random Allocation