Hair follicle miRNAs: a novel biomarker for primary blast Induced-Mild traumatic brain injury

Zhang, Jing; Knight, Rosalinda; Wang, Yushan; Sawyer, Thomas W.; Martyniuk, Christopher J.; Langlois, Valérie S.

doi:10.1080/1354750x.2018.1531929

Cited by 7 publications

(4 citation statements)

References 55 publications

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“…A biomarker test that was FDA-approved in 2018, known as The Brain Trauma Indicator, measures acute levels of UCH-L1 and GFAP in concussed individuals and provides the hope of reducing the need for unnecessary CT scans by prediction of intracranial lesions ( 132 ). A less mainstream approach to identify biomarkers involves the study of mammalian hair follicles that demonstrated unique subnetworks of miRNA following mTBI ( 133 ). As considerable inconsistencies exist pertaining to blast TBI, one of the main research goals of preclinical blast TBI studies is to aid the development of assays for highly reliable blood biomarkers.…”

Section: Biomarker Development and Treatment Approaches For Blast-induced Tbimentioning

confidence: 99%

Perspectives on Primary Blast Injury of the Brain: Translational Insights Into Non-inertial Low-Intensity Blast Injury

et al. 2022

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Most traumatic brain injuries (TBIs) during military deployment or training are clinically “mild” and frequently caused by non-impact blast exposures. Experimental models were developed to reproduce the biological consequences of high-intensity blasts causing moderate to severe brain injuries. However, the pathophysiological mechanisms of low-intensity blast (LIB)-induced neurological deficits have been understudied. This review provides perspectives on primary blast-induced mild TBI models and discusses translational aspects of LIB exposures as defined by standardized physical parameters including overpressure, impulse, and shock wave velocity. Our mouse LIB-exposure model, which reproduces deployment-related scenarios of open-field blast (OFB), caused neurobehavioral changes, including reduced exploratory activities, elevated anxiety-like levels, impaired nesting behavior, and compromised spatial reference learning and memory. These functional impairments associate with subcellular and ultrastructural neuropathological changes, such as myelinated axonal damage, synaptic alterations, and mitochondrial abnormalities occurring in the absence of gross- or cellular damage. Biochemically, we observed dysfunctional mitochondrial pathways that led to elevated oxidative stress, impaired fission-fusion dynamics, diminished mitophagy, decreased oxidative phosphorylation, and compensated cell respiration-relevant enzyme activity. LIB also induced increased levels of total tau, phosphorylated tau, and amyloid β peptide, suggesting initiation of signaling cascades leading to neurodegeneration. We also compare translational aspects of OFB findings to alternative blast injury models. By scoping relevant recent research findings, we provide recommendations for future preclinical studies to better reflect military-operational and clinical realities. Overall, better alignment of preclinical models with clinical observations and experience related to military injuries will facilitate development of more precise diagnosis, clinical evaluation, treatment, and rehabilitation.

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Section: Biomarker Development and Treatment Approaches For Blast-induced Tbimentioning

confidence: 99%

Perspectives on Primary Blast Injury of the Brain: Translational Insights Into Non-inertial Low-Intensity Blast Injury

et al. 2022

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“…Several miRNAs were upregulated or downregulated in injured versus control mice21 and changes in miR-21 occurred between TBI severities 22. One study assessed mammalian hair follicle miRNAs (rat whiskers) as an mTBI biomarker and found that 6 miRNAs within TBI molecular networks were disrupted after TBI23 (see Table 1, see Supplemental Digital Content Table 4, available at: http://links.lww.com/JHTR/A373).…”

Section: Resultsmentioning

confidence: 99%

miRNAs as Potential Biomarkers for Traumatic Brain Injury: Pathway From Diagnosis to Neurorehabilitation

Herrold

Kletzel

Foecking

et al. 2020

Journal of Head Trauma Rehabilitation

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Background: Biomarkers that can advance precision neurorehabilitation of the traumatic brain injury (TBI) are needed. MicroRNAs (miRNAs) have biological properties that could make them well suited for playing key roles in differential diagnoses and prognoses and informing likelihood of responsiveness to specific treatments. Objective: To review the evidence of miRNA alterations after TBI and evaluate the state of science relative to potential neurorehabilitation applications of TBI-specific miRNAs. Methods: This scoping review includes 57 animal and human studies evaluating miRNAs after TBI. PubMed, Scopus, and Google Scholar search engines were used. Results: Gold standard analytic steps for miRNA biomarker assessment are presented. Published studies evaluating the evidence for miRNAs as potential biomarkers for TBI diagnosis, severity, natural recovery, and treatmentinduced outcomes were reviewed including statistical evaluation. Growing evidence for specific miRNAs, including miR21, as TBI biomarkers is presented. Conclusions: There is evidence of differential miRNA expression in TBI in both human and animal models; however, gaps need to be filled in terms of replication using rigorous, standardized methods to isolate a consistent set of miRNA changes. Longitudinal studies in TBI are needed to understand how miRNAs could be implemented as biomarkers in clinical practice.

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“…The most downregulated miRNA at the 2-h timepoint (fold change−7.65), miR-181c-5p, maintained more than a 5-fold reduction after 18 h from concussion and almost 3-fold at the end of the season. Interestingly, one study reported that miR-181c-5p was part of miRNA signature for primary blast-induced mild TBI evaluated in hair follicles ( 46 ). We also found that miR-17-5p was significantly downregulated near or >3-fold at every timepoint, including the end of the season.…”

Section: Discussionmentioning

confidence: 99%

Serum microRNAs associated with concussion in football players

et al. 2023

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Mild Traumatic Brain Injury (mild TBI)/concussion is a common sports injury, especially common in football players. Repeated concussions are thought to lead to long-term brain damage including chronic traumatic encephalopathy (CTE). With the worldwide growing interest in studying sport-related concussion the search for biomarkers for early diagnosis and progression of neuronal injury has also became priority. MicroRNAs are short, non-coding RNAs that regulate gene expression post-transcriptionally. Due to their high stability in biological fluids, microRNAs can serve as biomarkers in a variety of diseases including pathologies of the nervous system. In this exploratory study, we have evaluated changes in the expression of selected serum miRNAs in collegiate football players obtained during a full practice and game season. We found a miRNA signature that can distinguish with good specificity and sensitivity players with concussions from non-concussed players. Furthermore, we found miRNAs associated with the acute phase (let-7c-5p, miR-16-5p, miR-181c-5p, miR-146a-5p, miR-154-5p, miR-431-5p, miR-151a-5p, miR-181d-5p, miR-487b-3p, miR-377-3p, miR-17-5p, miR-22-3p, and miR-126-5p) and those whose changes persist up to 4 months after concussion (miR-17-5p and miR-22-3p).

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Hair follicle miRNAs: a novel biomarker for primary blast Induced-Mild traumatic brain injury

Cited by 7 publications

References 55 publications

Perspectives on Primary Blast Injury of the Brain: Translational Insights Into Non-inertial Low-Intensity Blast Injury

Perspectives on Primary Blast Injury of the Brain: Translational Insights Into Non-inertial Low-Intensity Blast Injury

miRNAs as Potential Biomarkers for Traumatic Brain Injury: Pathway From Diagnosis to Neurorehabilitation

Serum microRNAs associated with concussion in football players

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