A Review of MicroRNA Biomarkers in Traumatic Brain Injury.
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ABSTRACT:
SUBMITTER: Atif H
PROVIDER: S-EPMC6410383 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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Project description:Biomarkers can be broadly defined as qualitative or quantitative measurements that convey information on the physiopathological state of a subject at a certain time point or disease state. Biomarkers can indicate health, pathology, or response to treatment, including unwanted side effects. When used as outcomes in clinical trials, biomarkers act as surrogates or substitutes for clinically meaningful endpoints. Biomarkers of disease can be diagnostic (the identification of the nature and cause of a condition) or prognostic (predicting the likelihood of a person's survival or outcome of a disease). In addition, genetic biomarkers can be used to quantify the risk of developing a certain disease. In the specific case of traumatic brain injury, surrogate blood biomarkers of imaging can improve the standard of care and reduce the costs of diagnosis. In addition, a prognostic role for biomarkers has been suggested in the case of post-traumatic epilepsy. Given the extensive literature on clinical biomarkers, we will focus herein on biomarkers which are present in peripheral body fluids such as saliva and blood. In particular, blood biomarkers, such as glial fibrillary acidic protein and salivary/blood S100B, will be discussed together with the use of nucleic acids (eg, DNA) collected from peripheral cells.
| S-EPMC6231511 | biostudies-literature
Project description:Traumatic brain injury (TBI) is a prominent global cause of mortality due to the limited availability of effective prevention and treatment strategies for this disorder. An effective molecular biomarker may contribute to determining the prognosis and promoting the therapeutic efficiency of TBI. MicroRNA-124 (miR-124) is most abundantly expressed in the brain and exerts different biological effects in a variety of diseases by regulating pathological processes of apoptosis and proliferation. Recently, increasing evidence has demonstrated the association between miR-124 and TBI, but there is still a lack of relevant literature to summarize the current evidence on this topic. Based on this review, we found that miR-124 was involved as a regulatory factor in cell apoptosis and proliferation, and was also strongly related with the pathophysiological development of TBI. MiR-124 played an essential role in TBI by interacting with multiple biomolecules and signaling pathways, such as JNK, VAMP-3, Rela/ApoE, PDE4B/mTOR, MDK/TLR4/NF-κB, DAPK1/NR2B, JAK/STAT3, PI3K/AKT, Ras/MEK/Erk. The potential benefits of upregulating miR-124 in facilitating TBI recovery have been identified. The advancement of miRNA nanocarrier system technology presents an opportunity for miR-124 to emerge as a novel therapeutic target for TBI. However, the specific mechanisms underlying the role of miR-124 in TBI necessitate further investigation. Additionally, comprehensive large-scale studies are required to evaluate the clinical significance of miR-124 as a therapeutic target for TBI.
| S-EPMC10687822 | biostudies-literature
Project description:Severe traumatic brain injury continues to present complex management and prediction challenges for the clinician. While there is some evidence that better systems of care can improve outcome, multiple multi-centre randomised controlled trials of specific therapies have consistently failed to show benefit. In addition, clinicians are challenged in attempting to accurately predict which children will recover well and which children will have severe and persisting neurocognitive deficits. Traumatic brain injury is vastly heterogeneous and so it is not surprising that one therapy or approach, when applied to a mixed cohort of children in a clinical trial setting, has yielded disappointing results. Children with severe traumatic brain injury have vastly different brain injury pathologies of widely varying severity, in any number of anatomical locations at what may be disparate stages of brain development. This heterogeneity may also explain why clinicians are unable to accurately predict outcome. Biomarkers are objective molecular signatures of injury that are released following traumatic brain injury and may represent a way of unifying the heterogeneity of traumatic brain injury into a single biosignature. Biomarkers hold promise to diagnose brain injury severity, guide intervention selection for clinical trials, or provide vital prognostic information so that early intervention and rehabilitation can be planned much earlier in the course of a child's recovery. Serum S100B and serum NSE levels show promise as a diagnostic tool with biomarker levels significantly higher in children with severe TBI including children with inflicted and non-inflicted head injury. Serum S100B and serum NSE also show promise as a predictor of neurodevelopmental outcome. The role of biomarkers in traumatic brain injury is an evolving field with the potential for clinical application within the next few years.
| S-EPMC8578762 | biostudies-literature
Project description:Traumatic brain injury (TBI) is increasingly a major cause of disability across the globe. The current methods of diagnosis are inadequate at classifying patients and prognosis. TBI is a diagnostic and therapeutic challenge. There is no Food and Drug Administration (FDA)-approved treatment for TBI yet. It took about 16 years of preclinical research to develop accurate and objective diagnostic measures for TBI. Two brain-specific protein biomarkers, namely, ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein, have been extensively characterized. Recently, the two biomarkers were approved by the FDA as the first blood-based biomarker, Brain Trauma Indicator™ (BTI™), via the Breakthrough Devices Program. This scoping review presents (i) TBI diagnosis challenges, (ii) the process behind the FDA approval of biomarkers, and (iii) known unknowns in TBI biomarker biology. The current lag in TBI incidence and hospitalization can be reduced if digital biomarkers such as hard fall detection are standardized and used as a mechanism to alert paramedics to an unresponsive trauma patient.
| S-EPMC8978594 | biostudies-literature
Project description:Traumatic brain injury (TBI) has a complex pathology in which the initial injury releases damage associated proteins that exacerbate the neuroinflammatory response during the chronic secondary injury period. One of the major pathological players in the inflammatory response after TBI is the inflammasome. Increased levels of inflammasome proteins during the acute phase after TBI are associated with worse functional outcomes. Previous studies reveal that the level of inflammasome proteins in biological fluids may be used as promising new biomarkers for the determination of TBI functional outcomes. In this study, we provide further evidence that inflammatory cytokines and inflammasome proteins in serum may be used to determine injury severity and predict pathological outcomes. In this study, we analyzed blood serum from TBI patients and respective controls utilizing Simple Plex inflammasome and V-PLEX inflammatory cytokine assays. We performed statistical analyses to determine which proteins were significantly elevated in TBI individuals. The receiver operating characteristics (ROC) were determined to obtain the area under the curve (AUC) to establish the potential fit as a biomarker. Potential biomarkers were then compared to documented patient Glasgow coma scale scores via a correlation matrix and a multivariate linear regression to determine how respective biomarkers are related to the injury severity and pathological outcome. Inflammasome proteins and inflammatory cytokines were elevated after TBI, and the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC), interleukin (IL)-18, tumor necrosis factor (TNF)-α, IL-4 and IL-6 were the most reliable biomarkers. Additionally, levels of these proteins were correlated with known clinical indicators of pathological outcome, such as the Glasgow coma scale (GCS). Our results show that inflammatory cytokines and inflammasome proteins are promising biomarkers for determining pathological outcomes after TBI. Additionally, levels of biomarkers could potentially be utilized to determine a patient's injury severity and subsequent pathological outcome. These findings show that inflammation-associated proteins in the blood are reliable biomarkers of injury severity that can also be used to assess the functional outcomes of TBI patients.
| S-EPMC9227014 | biostudies-literature
Project description:Circulating microRNAs (miRNAs) present in the serum/plasma are characteristically altered in many pathological conditions, and have been employed as diagnostic markers for specific diseases. We examined if plasma miRNA levels are altered in patients with traumatic brain injury (TBI) relative to matched healthy volunteers, and explored their potential for use as diagnostic TBI biomarkers. The plasma miRNA profiles from severe TBI patients (Glasgow Coma Scale [GCS] score ≤8) and age-, gender-, and race-matched healthy volunteers were compared by microarray analysis. Of the 108 miRNAs identified in healthy volunteer plasma, 52 were altered after severe TBI, including 33 with decreased and 19 with increased relative abundance. An additional 8 miRNAs were detected only in the TBI plasma. We used quantitative RT-PCR to determine if plasma miRNAs could identify TBI patients within the first 24 h post-injury. Receiver operating characteristic curve analysis indicated that miR-16, miR-92a, and miR-765 were good markers of severe TBI (0.89, 0.82, and 0.86 AUC values, respectively). Multiple logistic regression analysis revealed that combining these miRNAs markedly increased diagnostic accuracy (100% specificity and 100% sensitivity), compared to either healthy volunteers or orthopedic injury patients. In mild TBI patients (GCS score > 12), miR-765 levels were unchanged, while the plasma levels of miR-92a and miR-16 were significantly increased within the first 24 h of injury compared to healthy volunteers, and had AUC values of 0.78 and 0.82, respectively. Our results demonstrate that circulating miRNA levels are altered after TBI, providing a rich new source of potential molecular biomarkers. Plasma-derived miRNA biomarkers, used in combination with established clinical practices such as imaging, neurocognitive, and motor examinations, have the potential to improve TBI patient classification and possibly management.
| S-EPMC6468948 | biostudies-literature
Project description:BackgroundThe inflammasome plays an important role in the inflammatory innate immune response after central nervous system (CNS) injury. Inhibition of the inflammasome after traumatic brain injury (TBI) results in improved outcomes by lowering the levels of caspase-1 and interleukin (IL)-1b. We have previously shown that inflammasome proteins are elevated in the cerebrospinal fluid (CSF) of patients with TBI and that higher levels of these proteins were consistent with poorer outcomes after TBI when compared to patients that presented these inflammasome proteins at lower levels.Methods and findingsHere we extend our work by analyzing serum from 21 TBI patients and CSF from 18 TBI patients compared to 120 serum samples and 30 CSF samples from no-TBI donor controls for the expression of caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin(IL)-1b and IL-18. Analysis was carried out using the Ella Simple Plex system (Protein Simple) to determine the sensitivity and specificity of inflammasome proteins as biomarkers of TBI. Receiver operator characteristic (ROC) curves, confidence intervals and likelihood ratios for each biomarker was determined. ROC curves, confidence intervals, sensitivity and specificity for each biomarker examined revealed that caspase-1 (0.93 area under the curve (AUC)) and ASC (0.90 AUC) in serum and ASC (1.0 AUC) and IL-18 (0.84 AUC) in CSF are promising biomarkers of TBI pathology. Importantly, higher protein levels (above 547.6 pg/ml) of ASC (0.91 AUC) were consistent with poorer outcomes after TBI as determined by the Glasgow Outcome Scale-Extended (GOSE).ConclusionThese findings indicate that inflammasome proteins are excellent diagnostic and predictive biomarkers of TBI.
| S-EPMC6312377 | biostudies-literature
Project description:BackgroundDespite decades of research, outcomes in pediatric traumatic brain injury (pTBI) remain highly variable. Brain biofluid-specific biomarkers from pTBI patients may allow us to diagnose and prognosticate earlier and with a greater degree of accuracy than conventional methods. This manuscript reviews the evidence surrounding current brain-specific biomarkers in pTBI and assesses the temporal relationship between the natural history of the traumatic brain injury (TBI) and measured biomarker levels.MethodsA literature search was conducted in the Ovid, PubMed, MEDLINE, and Cochrane databases seeking relevant publications. The study selection and screening process were documented in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. Extraction forms included developmental stages of patients, type and biofluid source of biomarkers, brain injury type, and other relevant data.ResultsThe search strategy identified 443 articles, of which 150 examining the biomarkers of our interest were included. The references retrieved were examined thoroughly and discussed at length with a pediatric neurocritical care intensivist specializing in pTBI and a Ph.D. scientist with a high degree of involvement in TBI biomarker research, authoring a vast amount of literature in this field.ConclusionsTBI biomarkers might serve as valuable tools in the diagnosis and prognosis of pTBI. However, while each biomarker has its advantages, they are not without limitations, and therefore, further research is critical in pTBI biomarkers.
| S-EPMC9038667 | biostudies-literature
Project description:Purpose: The goal of this study is to investigate the expression of microRNAs in TBI biofluids compared to uninjured controls Methods: miRNA-Seq analysis of microRNA expression TBI and uninjured control biofluids
2020-03-09 | GSE131695 | GEO
Project description:Traumatic brain injury (TBI) is a clinical diagnosis of neurological dysfunction following head trauma, typically presenting with acute symptoms of some degree of cognitive impairment. There are an estimated 1.7 to 3.8 million TBIs each year in the United States, approximately 10 percent of which are due to sports and recreational activities. Most brain injuries are self-limited with symptom resolution within one week, however, a growing amount of data is now establishing significant sequelae from even minor impacts such as headaches, prolonged cognitive impairments, or even death. Appropriate diagnosis and treatment according to standardized guidelines are crucial when treating athletes who may be subjected to future head trauma, possibly increasing their likelihood of long-term impairments.
| S-EPMC3400421 | biostudies-literature