Derivation of a Three Biomarker Panel to Improve Diagnosis in Patients with Mild Traumatic Brain Injury

Peacock, W. Frank; Meter, Timothy E. Van; Mirshahi, Nazanin; Ferber, Kyle; Gerwien, Robert; Rao, Vani; Sair, Haris I.; Diaz‐Arrastia, Ramon; Korley, Frederick K.

doi:10.3389/fneur.2017.00641

Cited by 39 publications

(21 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It found that serum Ng levels in acute TBI patients are significantly higher than those in non-TBI controls, with a ROC of 0.72 for diagnosing TBI ( Yang et al, 2015 ). An observational emergency department study of head-injured and control patients also reached the consistent conclusions that Ng is elevated within 2–6 h after injury ( Peacock et al, 2017 ). A recent study aimed to explore the effect of TBI on Ng by detecting the protein expression at different time points after injury ( Svirsky et al, 2020 ).…”

Section: Associations Between Neurogranin and Neurological And Mentalmentioning

confidence: 76%

Neurogranin: A Potential Biomarker of Neurological and Mental Diseases

Xiang

Xin

Yang³

2020

Front. Aging Neurosci.

View full text Add to dashboard Cite

Neurogranin (Ng) is a small protein usually expressed in granule-like structures in pyramidal cells of the hippocampus and cortex. However, its clinical value is not fully clear so far. Currently, Ng is proved to be involved in synaptic plasticity, synaptic regeneration, and long-term potentiation mediated by the calcium- and calmodulin-signaling pathways. Due to both the synaptic integrity and function as the growing concerns in the pathogenesis of a wide variety of neurological and mental diseases, a series of researches published focused on the associations between Ng and these kinds of diseases in the past decade. Therefore, in this review, we highlight several diseases, which include, but are not limited to, Alzheimer’s disease, Parkinson disease, Creutzfeldt–Jakob disease, neuro-HIV, neurosyphilis, schizophrenia, depression, traumatic brain injury, and acute ischemic stroke, and summarize the associations between cerebrospinal fluid or blood-derived Ng with these diseases. We propose that Ng is a potential and promising biomarker to improve the diagnosis, prognosis, and severity evaluation of these diseases in the future.

show abstract

Section: Associations Between Neurogranin and Neurological And Mentalmentioning

confidence: 76%

Neurogranin: A Potential Biomarker of Neurological and Mental Diseases

Xiang

Xin

Yang³

2020

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…For example, serum levels of NF-L increase the first week after injury [29]. However, there are no in vivo studies that have fully assessed the serum half-life of NF-L. Another panel of three biomarkers, NSE, metallothionein 3, and neurogranin, were all identified in mild TBI patients during the first 6 hours after trauma [30]. Their levels in blood, however, were undetectable days after injury, and these markers require clinical validation.…”

Section: Discussionmentioning

confidence: 99%

Serum Amyloid A Protein as a Potential Biomarker for Severity and Acute Outcome in Traumatic Brain Injury

Wicker

Benton

George

et al. 2019

BioMed Research International

View full text Add to dashboard Cite

Traumatic brain injury (TBI) causes a wide variety of neuroinflammatory events. These neuroinflammatory events depend, to a greater extent, on the severity of the damage. Our previous studies have shown that the liver produces serum amyloid A (SAA) at high levels in the initial hours after controlled cortical impact (CCI) injury in mice. Clinical studies have reported detectable SAA in the plasma of brain injury patients, but it is not clear if SAA levels depend on TBI severity. To evaluate this question, we performed a mild to severe CCI injury in wild-type mice. We collected blood samples and brains at 1, 3, and 7 days after injury for protein detection by western blotting, enzyme-linked immunosorbent assay, or immunohistochemical analysis. Our results showed that severe CCI injury compared to mild CCI injury or sham mice caused an increased neuronal death, larger lesion volume, increased microglia/macrophage density, and augmented neutrophil infiltration. Furthermore, we found that the serum levels of SAA protein ascended in the blood in correlation with high neuroinflammatory and neurodegenerative responses. Altogether, these results suggest that serum SAA may be a novel neuroinflammation-based, and severity-dependent, biomarker for acute TBI.

show abstract

“…For example, in biofluid biomarkers, a panel of multiple glial, neuronal, metabolism, inflammatory, and microRNA biomarkers seems to be a more appropriate approach to identify and assess the severity, timing and pattern of injury. The concept of using multivariate biofluid biomarkers for TBI is growing and several clinical studies showed superiority of multivariate biofluid biomarker over single biomarker for TBI ( Beers et al, 2007 ; Diaz-Arrastia et al, 2014 ; Hajiaghamemar et al, 2017 ; Lo et al, 2009 ; Peacock et al, 2017 ). In addition, a panel of different EEG features or scores have shown promise as a potential tool to detect and monitor concussion ( Jacquin et al, 2018 ; Kiefer et al, 2015 ).…”

Section: Translational Challenges and Pathways For Explorationmentioning

confidence: 99%

Toward development of clinically translatable diagnostic and prognostic metrics of traumatic brain injury using animal models: A review and a look forward

Hajiaghamemar

Seidi

Oeur

et al. 2019

Experimental Neurology

View full text Add to dashboard Cite

Traumatic brain injury is a leading cause of cognitive and behavioral deficits in children in the US each year. There is an increasing interest in both clinical and pre-clinical studies to discover biomarkers to accurately diagnose traumatic brain injury (TBI), predict its outcomes, and monitor its progression especially in the developing brain. In humans, the heterogeneity of TBI in terms of clinical presentation, injury causation, and mechanism has contributed to the many challenges associated with finding unifying diagnosis, treatment, and management practices. In addition, findings from adult human research may have little application to pediatric TBI, as age and maturation levels affect the injury biomechanics and neurophysiological consequences of injury. Animal models of TBI are vital to address the variability and heterogeneity of TBI seen in human by isolating the causation and mechanism of injury in reproducible manner. However, a gap between the pre-clinical findings and clinical applications remains in TBI research today. To take a step toward bridging this gap, we reviewed several potential TBI tools such as biofluid biomarkers, electroencephalography (EEG), actigraphy, eye responses, and balance that have been explored in both clinical and pre-clinical studies and have shown potential diagnostic, prognostic, or monitoring utility for TBI. Each of these tools measures specific deficits following TBI, is easily accessible, non/minimally invasive, and is potentially highly translatable between animals and human outcomes because they involve effort-independent and non-verbal tasks. Especially conspicuous is the fact that these biomarkers and techniques can be tailored for infants and toddlers. However, translation of preclinical outcomes to clinical applications of these tools necessitates addressing several challenges. Among the challenges are the heterogeneity of clinical TBI, age dependency of some of the biomarkers, different brain structure, life span, and possible variation between temporal profiles of biomarkers in human and animals. Conducting parallel clinical and pre-clinical research, in addition to the integration of findings across species from several pre-clinical models to generate a spectrum of TBI mechanisms and severities is a path toward overcoming some of these challenges. This effort is possible through large scale collaborative research and data sharing across multiple centers. In addition, TBI causes dynamic deficits in multiple domains, and thus, a panel of biomarkers combining these measures to consider different deficits is more promising than a single biomarker for TBI. In this review, each of these tools are presented along with the clinical and pre-clinical findings, advantages, challenges and prospects of translating the pre-clinical knowledge into the human clinical setting.

show abstract

Derivation of a Three Biomarker Panel to Improve Diagnosis in Patients with Mild Traumatic Brain Injury

Cited by 39 publications

References 43 publications

Neurogranin: A Potential Biomarker of Neurological and Mental Diseases

Neurogranin: A Potential Biomarker of Neurological and Mental Diseases

Serum Amyloid A Protein as a Potential Biomarker for Severity and Acute Outcome in Traumatic Brain Injury

Toward development of clinically translatable diagnostic and prognostic metrics of traumatic brain injury using animal models: A review and a look forward

Contact Info

Product

Resources

About