| BACKGROUND: An accelerated speed of fracture-healing in patients with traumatic brain injury (TBI) is often encountered in our clinical practice. However the mechanisms responsible for this phenomenon are remain unclear. After TBI, many cytokines or peptides change their expressions. Calcitonin gene-related peptide (CGRP) is a neuropeptide which increases dramatically after brain injury. Also CGRP has an osteogenic stimulating effect. Therefore,we presume that CGRP may play a great part in accelerated fracture-healing. To test the hypothesis that the TBI causes the changes of CGRP level in serum that enhances fracture-healing, we established a reproducible animal model of TBI in association with a standard closed fracture, and measured the speed of fracture-healing and detected the expression of CGRP in serum, brain tissues and muscles surrounding the fracture sites. 1. Establishment and evaluation of a new type model of closed fracture in ratsOBJECTIVE: To develop a standard closed experimental fracture of femur in rats,a device was made. METHOD: The left femur was treated with retrograde Kirschner wire in Sprague-Dawley rats.The femoral diaphysis was then fractured by a fracture apparatus designed by ourselves. At 1,4,8 weeks after operation, left femurs were harvested. Fracture patterns, displacement and fracture-healing were assessed by using X-ray and histological test. RESULTS: X-ray test revealed that short-oblique or transverse fractures and with no obvious displacement, accounted for 86.1 % of all fractured bones. Histologically, there was a typical fracture union by secondary intention. CONCLUSIONS: A highly reproducible and less external factors influenced standard closed fracture model is established by our designed apparatus.2. An animal model of traumatic brain injury and its related evaluating systemOBJECTIVE: To prepare a device for animal model of traumatic brain injury and establish a system of evaluation. METHOD: A weight-drop device was made to establish models of TBI in rats. Vital signs and pathological changes were observed. The changes of function were scored by a functional scale provided by us. RESULTS: After TBI, changes of vital signs were obvious, which was including apnea and hyperpnea, etc. Six hours after injury, experimental rats presented typical pathological changes of TBI. Twelve hours after injury, remarkable functional changes of cerebellum, brain stem and cerebrum were observed by our functional scale of nervous system. CONCLUSIONS: Our injury system can be used to produce and evaluate TBI models in rats.3. The role of calcitonin gene-related peptide in fracture-healing in association with traumatic brain injuryOBJECTIVE: To analyze the role of calcitonin gene-related peptide in fracture-healing in association with traumatic brain injury through standard models of closed fracture of femur and traumatic brain injury in rats. METHOD: A standard closed femoral fracture was produced in Sprague-Dawley rats which were subjected to additional closed head trauma that produced diffuse axonal injury similar to that observed in patients with a TBI. Four and eight weeks after the procedure, the animals were killed and fracture-healing was assessed by micro-CT analysis. Sera, brain tissues and muscles surrounding the fracture sites from the animals harvested at different time points were used to detect the expression of CGRP by ELISA analysis, immunohistochemistry assay, western blot analysis and RT-PCR analysis. RESULTS: Micro-CT analysis demonstrated that fracture-healing and mineralization in TBI-fracture group occurred earlier as compared to the fracture-only group. ELISA analysis indicated a high concentration of CGRP in TBI-fracture group (P<0.05), and all immunohistochemistry assay, western blot and RT-PCR analysis showed a significant increase of CGRP in the brain and muscle of TBI-fracture group at one week after fracture (P<0.001). This effect was not observed in the other groups. CONCLUSIONS: These results support data from previous studies that have suggested an enhancement of fracture-healing secondary to traumatic brain injury. Our results further suggest that the mechanism for this enhancement is related to the high level of CGRP which was released from brain tissue to the serum.
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