Bioinformatic analysis of brain-specific miRNAs for identification of candidate traumatic brain injury blood biomarkers

O’Connell, Grant; Smothers, Christine G.; Winkelman, Chris

doi:10.1080/02699052.2020.1764102

Cited by 31 publications

(31 citation statements)

References 45 publications

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“…Furthermore, miR-124-3p was detected only in patients with severe TBI ( Schindler et al, 2020 ). The miR-124-3p level was elevated in the serum of patients with TBI ( O’connell et al, 2020 ). However, miR-124-3p was downregulated in post-TBI hippocampal pathologies in experimental models and in humans ( Vuokila et al, 2018 ).…”

Section: Microrna-124 and Central Nervous System Traumamentioning

confidence: 99%

MicroRNA-124: A Key Player in Microglia-Mediated Inflammation in Neurological Diseases

Zhao

Wang

2021

Front. Cell. Neurosci.

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Neurological disorders are mainly characterized by progressive neuron loss and neurological deterioration, which cause human disability and death. However, many types of neurological disorders have similar pathological mechanisms, including the neuroinflammatory response. Various microRNAs (miRs), such as miR-21, miR-124, miR-146a, and miR-132 were recently shown to affect a broad spectrum of biological functions in the central nervous system (CNS). Microglia are innate immune cells with important roles in the physiological and pathological activities of the CNS. Recently, abnormal expression of miR-124 was shown to be associated with the occurrence and development of various diseases in CNS via regulating microglia function. In addition, miR-124 is a promising biomarker and therapeutic target. Studies on the role of miR-124 in regulating microglia function involved in pathogenesis of neurological disorders at different stages will provide new ideas for the use of miR-124 as a therapeutic target for different CNS diseases.

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Section: Microrna-124 and Central Nervous System Traumamentioning

confidence: 99%

MicroRNA-124: A Key Player in Microglia-Mediated Inflammation in Neurological Diseases

Zhao

Wang

2021

Front. Cell. Neurosci.

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“…Furthermore, our analysis could also be modified to identify other brain-enriched molecular species which could serve similar diagnostic function as the candidate proteins described here. For example, similar algorithmic analysis of publicly available micro-RNA (miRNA) datasets could be used to identify brain-enriched miRNAs (63), which may be beneficial in that miRNAs originating from the brain may be more detectable in the blood than proteins, given that they can be measured via PCR-based methods. Likewise, the gene expression datasets used in our analysis could be used to informatically predict brainenriched metabolites (64); if this information were combined with other existing disease-specific gene expression datasets, it may be possible to identify blood-borne brain-originating metabolites with a high degree of disease specificity.…”

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confidence: 99%

Large-scale informatic analysis to algorithmically identify blood biomarkers of neurological damage

O’Connell

Alder

Smothers

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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The identification of precision blood biomarkers which can accurately indicate damage to brain tissue could yield molecular diagnostics with the potential to improve how we detect and treat neurological pathologies. However, a majority of candidate blood biomarkers for neurological damage that are studied today are proteins which were arbitrarily proposed several decades before the advent of high-throughput omic techniques, and it is unclear whether they represent the best possible targets relative to the remainder of the human proteome. Here, we leveraged mRNA expression data generated from nearly 12,000 human specimens to algorithmically evaluate over 17,000 protein-coding genes in terms of their potential to produce blood biomarkers for neurological damage based on their expression profiles both across the body and within the brain. The circulating levels of proteins associated with the top-ranked genes were then measured in blood sampled from a diverse cohort of patients diagnosed with a variety of acute and chronic neurological disorders, including ischemic stroke, hemorrhagic stroke, traumatic brain injury, Alzheimer’s disease, and multiple sclerosis, and evaluated for their diagnostic performance. Our analysis identifies several previously unexplored candidate blood biomarkers of neurological damage with possible clinical utility, many of which whose presence in blood is likely linked to specific cell-level pathologic processes. Furthermore, our findings also suggest that many frequently cited previously proposed blood biomarkers exhibit expression profiles which could limit their diagnostic efficacy.

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“…Data indicate that miR-21, miR-92, and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and a useful tool for postmortem diagnosis of traumatic brain injury [104]. More recently, miR-124-3p, miR-219a-5p, miR-9-5p, miR-9-3p, miR-137, and miR-128-3p exhibited dramatically greater brain specificity as blood biomarkers of TBI [105].…”

Section: Discussionmentioning

confidence: 99%

Post-Traumatic Meningitis Is a Diagnostic Challenging Time: A Systematic Review Focusing on Clinical and Pathological Features

Russa

Maiese

Fazio

et al. 2020

IJMS

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Post-traumatic meningitis is a dreadful condition that presents additional challenges, in terms of both diagnosis and management, when compared with community-acquired cases. Post-traumatic meningitis refers to a meningeal infection causally related to a cranio-cerebral trauma, regardless of temporal proximity. The PICO (participants, intervention, control, and outcomes) question was as follows: “Is there an association between traumatic brain injury and post-traumatic meningitis?” The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. Studies examining post-traumatic meningitis, paying particular attention to victims of traumatic brain injury, were included. Post-traumatic meningitis represents a high mortality disease. Diagnosis may be difficult both because clinical signs are nonspecific and blurred and because of the lack of pathognomonic laboratory markers. Moreover, these markers increase with a rather long latency, thus not allowing a prompt diagnosis, which could improve patients’ outcome. Among all the detectable clinical signs, the appearance of cranial cerebrospinal fluid (CSF) leakage (manifesting as rhinorrhea or otorrhea) should always arouse suspicion of meningitis. On one hand, microbiological exams on cerebrospinal fluid (CSF), which represent the gold standard for the diagnosis, require days to get reliable results. On the other hand, radiological exams, especially CT of the brain, could represent an alternative for early diagnosis. An update on these issues is certainly of interest to focus on possible predictors of survival and useful tools for prompt diagnosis.

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Bioinformatic analysis of brain-specific miRNAs for identification of candidate traumatic brain injury blood biomarkers

Cited by 31 publications

References 45 publications

MicroRNA-124: A Key Player in Microglia-Mediated Inflammation in Neurological Diseases

MicroRNA-124: A Key Player in Microglia-Mediated Inflammation in Neurological Diseases

Large-scale informatic analysis to algorithmically identify blood biomarkers of neurological damage

Post-Traumatic Meningitis Is a Diagnostic Challenging Time: A Systematic Review Focusing on Clinical and Pathological Features

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