Elevated concentrations of hypoxia-inducible factor-1α in patients with fracture and concomitant traumatic brain injury

2016 ◽  
Vol 54 (5) ◽  
pp. 584-592 ◽  
Author(s):  
Xiguang Sang ◽  
Zhiyong Wang ◽  
Tao Qin ◽  
Yonggang Li
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Fracture Healing ◽  
Bone Fracture ◽  
Hypoxia Inducible Factor ◽  
Fracture Repair ◽  
Long Bone ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Hypoxia Inducible Factor 1Α

Background Compelling evidence indicate that traumatic brain injury is highly related to accelerated bone fracture repair, but the underlying mechanism still remains elusive. Fracture repair process relies greatly on the formation of new blood vessels in fracture site, and angiogenic factors have been confirmed to be essential for the initiation and maintenance of the fracture healing. Hypoxia-inducible factor-1α was demonstrated to be a critical regulator of angiogenic–osteogenic coupling during bone development and regeneration. The aim of the present study was to investigate the local and circulating concentrations of hypoxia-inducible factor-1α in patients with long-bone fractures and concomitant traumatic brain injury and to determine the potential role of hypoxia-inducible factor-1α in fracture healing. Methods Twenty-five patients with a long-bone fracture and concomitant traumatic brain injury (FT group) and 33 without a brain injury (Fr group) were enrolled in this study. Healthy subjects donated serum samples as control. Serum samples were collected over a period of six months, following a standardized time schedule. Hypoxia-inducible factor-1α concentrations were measured in fracture haematoma and serum of patients in both groups using enzyme-linked immunosorbent assay. Results Patients in FT group had a short time to union. Serum hypoxia-inducible factor-1α concentrations elevated in the early healing period and reached the maximum level during intramembranous bone formation phase in both groups. Thereafter, it decreased continuously and approached to the minimum levels until the end of the observation period. Serum hypoxia-inducible factor-1α concentrations in both groups were significantly higher compared with controls and hypoxia-inducible factor-1α concentrations in both serum and fracture haematoma were higher in FT group than that in Fr group. Fracture haematoma contained significantly higher hypoxia-inducible factor-1α concentrations compared with hypoxia-inducible factor-1α concentrations in serum. Serum hypoxia-inducible factor-1α concentrations had a positive correlation with hypoxia-inducible factor-1α concentrations in fracture haematoma in patients with fractures. Conclusions These findings suggest the local and systemic involvement of hypoxia-inducible factor-1α in fracture healing and the accelerated fracture repair in patients with traumatic brain injury might be associated with elevated hypoxia-inducible factor-1α concentrations in fracture haematoma and serum.

scholarly journals Leptin Mediated Pathways Stabilize Posttraumatic Insulin and Osteocalcin Patterns after Long Bone Fracture and Concomitant Traumatic Brain Injury and Thus Influence Fracture Healing in a Combined Murine Trauma Model

2020 ◽  
Vol 21 (23) ◽  
pp. 9144
Author(s):  
Anja Garbe ◽  
Frank Graef ◽  
Jessika Appelt ◽  
Katharina Schmidt-Bleek ◽  
Denise Jahn ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Fracture Healing ◽  
Bone Fracture ◽  
Long Bone ◽  
Mouse Strains ◽  
Leptin Deficiency ◽  
Long Bone Fracture ◽  
Trauma Model ◽  
Deficient Mice

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.

scholarly journals Systemic and local cardiac inflammation after experimental long bone fracture, traumatic brain injury and combined trauma in mice

2021 ◽  
Vol 28 ◽  
pp. 39-46
Author(s):  
Ina Lackner ◽  
Birte Weber ◽  
Melanie Haffner-Luntzer ◽  
Simona Hristova ◽  
Florian Gebhard ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Bone Fracture ◽  
Long Bone ◽  
Cardiac Inflammation ◽  
Long Bone Fracture

scholarly journals RETRACTED: Synapse loss regulated by matrix metalloproteinases in traumatic brain injury is associated with hypoxia inducible factor-1α expression

2009 ◽  
Vol 1268 ◽  
pp. 125-134 ◽  
Author(s):  
Jamie Y. Ding ◽  
Christian W. Kreipke ◽  
Patrick Schafer ◽  
Steven Schafer ◽  
Susan L. Speirs ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Matrix Metalloproteinases ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1Α ◽  
Synapse Loss

scholarly journals Hypoxia-Inducible Factor 1 is Essential for Spontaneous Recovery from Traumatic Brain Injury and is a Key Mediator of Heat Acclimation Induced Neuroprotection

2013 ◽  
Vol 33 (4) ◽  
pp. 524-531 ◽  
Author(s):  
Gali Umschweif ◽  
Alexander G Alexandrovich ◽  
Victoria Trembovler ◽  
Michal Horowitz ◽  
Esther Shohami
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Motor Function ◽  
Spontaneous Recovery ◽  
Hypoxia Inducible Factor ◽  
Heat Acclimation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lesion Volume ◽  
Edema Formation ◽  
Glucose Transporter 1

Heat acclimation (HA), a well-established preconditioning model, confers neuroprotection in rodent models of traumatic brain injury (TBI). It increases neuroprotective factors, among them is hypoxia-inducible factor 1α (HIF-1α), which is important in the response to postinjury ischemia. However, little is known about the role of HIF-1α in TBI and its contribution to the establishment of the HA protecting phenotype. Therefore, we aimed to explore HIF-1α role in TBI defense mechanisms as well as in HA-induced neuroprotection. Acriflavine was used to inhibit HIF-1 in injured normothermic (NT) or HA mice. After TBI, we evaluated motor function recovery, lesion volume, edema formation, and body temperature as well as HIF-1 downstream transcription targets, such as glucose transporter 1 (GLUT1), vascular endothelial growth factor, and aquaporin 4. We found that HIF-1 inhibition resulted in deterioration of motor function, increased lesion volume, hypothermia, and reduced edema formation. All these parameters were significantly different in the HA mice. Western blot analysis and enzyme-linked immunosorbent assay showed reduced levels of all HIF-1 downstream targets in HA mice, however, only GLUT1 was downregulated in NT mice. We conclude that HIF-1 is a key mediator in both spontaneous recovery and HA-induced neuroprotection after TBI.

scholarly journals Hypoxia-inducible factor-1α signaling in aquaporin upregulation after traumatic brain injury

2009 ◽  
Vol 453 (1) ◽  
pp. 68-72 ◽  
Author(s):  
Jamie Y. Ding ◽  
Christian W. Kreipke ◽  
Susan L. Speirs ◽  
Patrick Schafer ◽  
Steven Schafer ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1Α

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

2019 ◽  
Vol 36 (4) ◽  
pp. 609-618 ◽  
Author(s):  
Yujin Suto ◽  
Katsuhiro Nagata ◽  
Syed M. Ahmed ◽  
Christina L. Jacovides ◽  
Kevin D. Browne ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cerebral Edema ◽  
Bone Fracture ◽  
Neurological Recovery ◽  
Long Bone ◽  
Long Bone Fracture

Dual Role of Caveolin-1 in β-Catenin Signaling During Fracture Healing Induced by Low-Intensity Pulsed Ultrasound in Rabbits

2021 ◽  
Vol 11 (2) ◽  
pp. 229-239
Author(s):  
Yun Li ◽  
Guanghua Liu ◽  
Feng Xiao ◽  
Wenqin Gu ◽  
Zhengdong Gao ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Molecular Mechanisms ◽  
Dual Role ◽  
Fracture Repair ◽  
Long Bone ◽  
Pulsed Ultrasound ◽  
Mineral Density ◽  
X Ray ◽  
Caveolin 1 ◽  
The Right

We did this research to observe the effect of LIPUS on long bone fracture repair and caveolin-1, β-catenin signaling expression in the radius defects of rabbits, to explore its possible molecular mechanisms. 24 male New Zealand rabbits with bilateral radial bone defects were divided into 4 groups randomly, n = 6. The right side had daily LIPUS exposure for 20 minutes, while the left received sham treatment. After 7, 14, 21, 28 days, respectively, fracture healing was observed by X-ray imaging and Dual Energy X-ray Absorptiometry (DXA) scan, specimens were harvested for histology, immunohistochemistry, and gene expression analysis. We found that LIPUS brought forward endochondral ossification, increased the bone callus size without changes in Bone Mineral Density (BMD). The caveolin-1 expression increased first then decreased, while the β-catenin kept growing during the process. These demonstrated that caveolin-1 participated in fracture healing accelerated by LIPUS, which was speculated to play a dual role in β-catenin signaling expression.

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