The role of serum Dickkopf‐1 in predicting 30‐day death in severe traumatic brain injury

Xia, Ke; Yang, Ming; Luo, Jing; Chen, Xiaoyu

doi:10.1002/brb3.1589

Cited by 4 publications

(3 citation statements)

References 28 publications

(43 reference statements)

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“…DKK1 serum concentration has been reported to correlate with TBI severity and 30-day mortality. 63 Here, we report a suggested biphasic dynamic of the protein with an early small peak at day 1, followed by a small dip in level on day 2, and then a distinct increase from day 3 to day 6 with a tapering off of the increase to day 7. This could be a sign of an increase over time for a certain aspect of the immune response to the injury.…”

Section: Discussionmentioning

confidence: 56%

A Dedicated 21-Plex Proximity Extension Assay Panel for High-Sensitivity Protein Biomarker Detection Using Microdialysis in Severe Traumatic Brain Injury: The Next Step in Precision Medicine?

Dyhrfort

Wettervik

Clausen

et al. 2023

Neurotrauma Reports

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Cerebral protein profiling in traumatic brain injury (TBI) is needed to better comprehend secondary injury pathways. Cerebral microdialysis (CMD), in combination with the proximity extension assay (PEA) technique, has great potential in this field. By using PEA, we have previously screened >500 proteins from CMD samples collected from TBI patients. In this study, we customized a PEA panel prototype of 21 selected candidate protein biomarkers, involved in inflammation (13), neuroplasticity/-repair (six), and axonal injury (two). The aim was to study their temporal dynamics and relation to age, structural injury, and clinical outcome. Ten patients with severe TBI and CMD monitoring, who were treated in the Neurointensive Care Unit, Uppsala University Hospital, Sweden, were included. Hourly CMD samples were collected for up to 7 days after trauma and analyzed with the 21-plex PEA panel. Seventeen of the 21 proteins from the CMD sample analyses showed significantly different mean levels between days. Early peaks (within 48 h) were noted with interleukin (IL)-1β, IL-6, IL-8, granulocyte colony-stimulating factor, transforming growth factor alpha, brevican, junctional adhesion molecule B, and neurocan. C-X-C motif chemokine ligand 10 peaked after 3 days. Late peaks (>5 days) were noted with interleukin-1 receptor antagonist (IL-1ra), monocyte chemoattractant protein (MCP)-2, MCP-3, urokinase-type plasminogen activator, Dickkopf-related protein 1, and DRAXIN. IL-8, neurofilament heavy chain, and TAU were biphasic. Age (above/below 22 years) interacted with the temporal dynamics of IL-6, IL-1ra, vascular endothelial growth factor, MCP-3, and TAU. There was no association between radiological injury (Marshall grade) or clinical outcome (Extended Glasgow Outcome Scale) with the protein expression pattern. The PEA method is a highly sensitive molecular tool for protein profiling from cerebral tissue in TBI. The novel TBI dedicated 21-plex panel showed marked regulation of proteins belonging to the inflammation, plasticity/repair, and axonal injury families. The method may enable important insights into complex injury processes on a molecular level that may be of value in future efforts to tailor pharmacological TBI trials to better address specific disease processes and optimize timing of treatments.

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Section: Discussionmentioning

confidence: 56%

A Dedicated 21-Plex Proximity Extension Assay Panel for High-Sensitivity Protein Biomarker Detection Using Microdialysis in Severe Traumatic Brain Injury: The Next Step in Precision Medicine?

Dyhrfort

Wettervik

Clausen

et al. 2023

Neurotrauma Reports

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“…In a recent study, it was reported that the levels of Dkk1 were elevated in the serum of patients with severe TBI (Ke et al, 2020). Importantly, Dkk1 elevated levels in the serum were closely associated with increasing severity of the trauma and higher risk of short-term mortality (Ke et al, 2020). Furthermore another study has reported that RHOA was upregulated as early as 24 h after trauma, persisting for several months after TBI (Brabeck et al, 2004).…”

Section: Implication In Tbi Pathobiologymentioning

confidence: 98%

“…Investigations into the implication of the Wnt pathway in humans with TBI conditions have recently started. In a recent study, it was reported that the levels of Dkk1 were elevated in the serum of patients with severe TBI (Ke et al, 2020). Importantly, Dkk1 elevated levels in the serum were closely associated with increasing severity of the trauma and higher risk of short-term mortality (Ke et al, 2020).…”

Section: Implication In Tbi Pathobiologymentioning

confidence: 99%

Wnt Pathway: An Emerging Player in Vascular and Traumatic Mediated Brain Injuries

2020

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The Wnt pathway, which comprises the canonical and non-canonical pathways, is an evolutionarily conserved mechanism that regulates crucial biological aspects throughout the development and adulthood. Emergence and patterning of the nervous and vascular systems are intimately coordinated, a process in which Wnt pathway plays particularly important roles. In the brain, Wnt ligands activate a cellspecific surface receptor complex to induce intracellular signaling cascades regulating neurogenesis, synaptogenesis, neuronal plasticity, synaptic plasticity, angiogenesis, vascular stabilization, and inflammation. The Wnt pathway is tightly regulated in the adult brain to maintain neurovascular functions. Historically, research in neuroscience has emphasized essentially on investigating the pathway in neurodegenerative disorders. Nonetheless, emerging findings have demonstrated that the pathway is deregulated in vascular-and traumatic-mediated brain injuries. These findings are suggesting that the pathway constitutes a promising target for the development of novel therapeutic protective and restorative interventions. Yet, targeting a complex multifunctional signal transduction pathway remains a major challenge. The review aims to summarize the current knowledge regarding the implication of Wnt pathway in the pathobiology of ischemic and hemorrhagic stroke, as well as traumatic brain injury (TBI). Furthermore, the review will present the strategies used so far to manipulate the pathway for therapeutic purposes as to highlight potential future directions.

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Enhancing motor functional recovery in spinal cord injury through pharmacological inhibition of Dickkopf-1 with BHQ880 antibody

González-Fernández,

González,

Maqueda

et al. 2024

Biomedicine & Pharmacotherapy

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The role of serum Dickkopf‐1 in predicting 30‐day death in severe traumatic brain injury

Abstract: Severe traumatic brain injury (sTBI) is a devastating type of trauma that is characterized by higher morbidity and mortality (Iaccarino,

Cited by 4 publications

References 28 publications

A Dedicated 21-Plex Proximity Extension Assay Panel for High-Sensitivity Protein Biomarker Detection Using Microdialysis in Severe Traumatic Brain Injury: The Next Step in Precision Medicine?

A Dedicated 21-Plex Proximity Extension Assay Panel for High-Sensitivity Protein Biomarker Detection Using Microdialysis in Severe Traumatic Brain Injury: The Next Step in Precision Medicine?

Wnt Pathway: An Emerging Player in Vascular and Traumatic Mediated Brain Injuries

Enhancing motor functional recovery in spinal cord injury through pharmacological inhibition of Dickkopf-1 with BHQ880 antibody

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