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

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 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 ELEVATION OF MATRIX METALLOPROTEINASES 3 AND 9 IN CEREBROSPINAL FLUID AND BLOOD IN PATIENTS WITH SEVERE TRAUMATIC BRAIN INJURY

Neurosurgery ◽  
2009 ◽  
Vol 65 (4) ◽  
pp. 702-708 ◽  
Author(s):  
Mark Grossetete ◽  
Jeremy Phelps ◽  
Leopold Arko ◽  
Howard Yonas ◽  
Gary A. Rosenberg
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Brain Injury ◽  
Matrix Metalloproteinases ◽  
Blood Brain Barrier ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Brain Barrier ◽  
Western Immunoblot ◽  
Blood Brain

Abstract OBJECTIVE Traumatic brain injury (TBI) causes an increase in matrix metalloproteinases (MMPs), which are associated with neuroinflammation, blood-brain barrier disruption, hemorrhage, and cell death. We hypothesized that patients with TBI have an increase in MMPs in ventricular cerebrospinal fluid (CSF) and plasma. METHODS Patients with TBI and a ventricular catheter were entered into the study. Samples of CSF and plasma were collected at the time of catheter placement and at 24 and 72 hours after admission. Seven TBI patients were entered into the study, with 6 having complete data for analysis. Only patients who had a known time of insult that fell within a 6-hour window from initial insult to ventriculostomy were accepted into the study. Control CSF came from ventricular fluid in patients undergoing shunt placement for normal pressure hydrocephalus. Both MMP-2 and MMP-9 were measured with gelatin zymography and MMP-3 with Western immunoblot. RESULTS We found a significant elevation in the levels of the latent form of MMP-9 (92-kD) in the CSF obtained at the time of arrival (P < 0.05). Elevated levels of MMP-2 were detected in plasma at 72 hours, but not in the CSF. Using albumin from both CSF and blood, we calculated the MMP-9 index, which was significantly increased in the CSF, indicating endogenous MMP production. Western immunoblot showed elevated levels of MMP-3 in CSF at all times measured, whereas MMP-3 was not detected in the CSF of normal pressure hydrocephalus. CONCLUSION We show that MMPs are increased in the CSF of TBI patients. Although the number of patients was small, the results were robust and clearly demonstrated increases in MMP-3 and MMP-9 in ventricular CSF in TBI patients compared with controls. Although these preliminary results will need to be replicated, we propose that MMPs may be important in blood-brain barrier opening and hemorrhage secondary to brain injury in patients.

scholarly journals Dynamics of cerebrospinal fluid levels of matrix metalloproteinases in human traumatic brain injury

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Karolina Minta ◽  
Gunnar Brinkmalm ◽  
Faiez Al Nimer ◽  
Eric P. Thelin ◽  
Fredrik Piehl ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Brain Injury ◽  
Matrix Metalloproteinases ◽  
Clinical Outcomes ◽  
Extracellular Enzymes ◽  
Tissue Injury ◽  
Normal Pressure ◽  
Magnetic Bead ◽  
Contrast Group

Abstract Matrix metalloproteinases (MMPs) are extracellular enzymes involved in the degradation of extracellular matrix (ECM) proteins. Increased expression of MMPs have been described in traumatic brain injury (TBI) and may contribute to additional tissue injury and blood–brain barrier damage. The objectives of this study were to determine longitudinal changes in cerebrospinal fluid (CSF) concentrations of MMPs after acute TBI and in relation to clinical outcomes, with patients with idiopathic normal pressure hydrocephalus (iNPH) serving as a contrast group. The study included 33 TBI patients with ventricular CSF serially sampled, and 38 iNPH patients in the contrast group. Magnetic bead-based immunoassays were utilized to measure the concentrations of eight MMPs in ventricular human CSF. CSF concentrations of MMP-1, MMP-3 and MMP-10 were increased in TBI patients (at baseline) compared with the iNPH group (p < 0.001), while MMP-2, MMP-9 and MMP-12 did not differ between the groups. MMP-1, MMP-3 and MMP-10 concentrations decreased with time after trauma (p = 0.001–0.04). Increased concentrations of MMP-2 and MMP-10 in CSF at baseline were associated with an unfavourable TBI outcome (p = 0.002–0.02). Observed variable pattern of changes in MMP concentrations indicates that specific MMPs serve different roles in the pathophysiology following TBI, and are in turn associated with clinical outcomes.

scholarly journals Traumatic glioblastoma: commentary and suggested mechanism

2018 ◽  
Vol 46 (6) ◽  
pp. 2170-2176
Author(s):  
Nissim Ohana ◽  
Daniel Benharroch ◽  
Dimitri Sheinis ◽  
Abraham Cohen
Keyword(s):  
Traumatic Brain Injury ◽  
Transcription Factors ◽  
Brain Injury ◽  
Brain Injuries ◽  
Hypoxia Inducible Factor ◽  
Subsequent Development ◽  
Factors Associated ◽  
The Relationship

The role of head trauma in the development of glioblastoma is highly controversial and has been minimized since first put forward. This is not unexpected because skull injuries are overwhelmingly more common than glioblastoma. This paper presents a commentary based on the contributions of James Ewing, who established a major set of criteria for the recognition of an official relationship between trauma and cancer. Ewing’s criteria were very stringent. The scholars who succeeded Ewing have facilitated the characterization of traumatic brain injuries since the introduction of computed tomography and magnetic resonance imaging. Discussions of the various criteria that have since developed are now being conducted, and those of an unnecessarily limiting nature are being highlighted. Three transcription factors associated with traumatic brain injury have been identified: p53, hypoxia-inducible factor-1α, and c-MYC. A role for these three transcription factors in the relationship between traumatic brain injury and glioblastoma is suggested; this role may support a cause-and-effect link with the subsequent development of glioblastoma.

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