A Review of MicroRNA Biomarkers in Traumatic Brain Injury

Atif, Hamna; Hicks, Steven D.

doi:10.1177/1179069519832286

Cited by 103 publications

(115 citation statements)

References 130 publications

(227 reference statements)

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“…The timing of sample collection relative to the concussion event is likely to have a large impact on miRNA profiles, when comparing these results with prior studies of miRNA levels in concussed individuals. Differences in biofluids of miRNA origin, methods for miRNA isolation, age of participants, and severity of head injury may also account for differences between our investigation and the results of previous studies [ 27 ].…”

Section: Discussionmentioning

confidence: 72%

“…Epigenetic mechanisms have the ability to alter cellular function in response to an external insult, and have been implicated in the chronic effects of mild traumatic brain injury [ 25 ]. Microribonucleic acids (miRNAs) are small epitranscriptional molecules that are critical to neuronal function [ 26 ], and regulate gene expression in response to traumatic brain injury [ 27 , 28 ]. Neurons have the ability to package miRNAs within protective exosomes as an intracellular signaling mechanism [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

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Saliva microRNA Biomarkers of Cumulative Concussion

Hicks

Olympia

Onks

et al. 2020

IJMS

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Recurrent concussions increase risk for persistent post-concussion symptoms, and may lead to chronic neurocognitive deficits. Little is known about the molecular pathways that contribute to persistent concussion symptoms. We hypothesized that salivary measurement of microribonucleic acids (miRNAs), a class of epitranscriptional molecules implicated in concussion pathophysiology, would provide insights about the molecular cascade resulting from recurrent concussions. This hypothesis was tested in a case-control study involving 13 former professional football athletes with a history of recurrent concussion, and 18 age/sex-matched peers. Molecules of interest were further validated in a cross-sectional study of 310 younger individuals with a history of no concussion (n = 230), a single concussion (n = 56), or recurrent concussions (n = 24). There was no difference in neurocognitive performance between the former professional athletes and their peers, or among younger individuals with varying concussion exposures. However, younger individuals without prior concussion outperformed peers with prior concussion on three balance assessments. Twenty salivary miRNAs differed (adj. p < 0.05) between former professional athletes and their peers. Two of these (miR-28-3p and miR-339-3p) demonstrated relationships (p < 0.05) with the number of prior concussions reported by younger individuals. miR-28-3p and miR-339-5p may play a role in the pathophysiologic mechanism involved in cumulative concussion effects.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Saliva microRNA Biomarkers of Cumulative Concussion

Hicks

Olympia

Onks

et al. 2020

IJMS

Self Cite

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“…However, these assays may enable future investigations of peripheral NLRP3 inflammasome proteins in the context of neuroinflammatory-related conditions. Furthermore, short non-coding strands of RNA termed microRNAs (miRNA) are receiving growing evidence as potential biomarkers of various CNS disorders including Alzheimer's disease, Parkinson's disease, and TBI [121,122]. miRNAs such as miR-223-3p are known regulators of the NLRP3 inflammasome and act at a priming and activation level of NLRP3 formation [123].…”

Section: Novel Biomarkers Of the Nlrp3 Inflammasomementioning

confidence: 99%

The NLRP3 inflammasome in traumatic brain injury: potential as a biomarker and therapeutic target

O’Brien

Pham

Symons

et al. 2020

J Neuroinflammation

153

108

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There is a great clinical need to identify the underlying mechanisms, as well as related biomarkers, and treatment targets, for traumatic brain injury (TBI). Neuroinflammation is a central pathophysiological feature of TBI. NLRP3 inflammasome activity is a necessary component of the innate immune response to tissue damage, and dysregulated inflammasome activity has been implicated in a number of neurological conditions. This paper introduces the NLRP3 inflammasome and its implication in the pathogenesis of neuroinflammatory-related conditions, with a particular focus on TBI. Although its role in TBI has only recently been identified, findings suggest that priming and activation of the NLRP3 inflammasome are upregulated following TBI. Moreover, recent studies utilizing specific NLRP3 inhibitors have provided further evidence that this inflammasome is a major driver of neuroinflammation and neurobehavioral disturbances following TBI. In addition, there is emerging evidence that circulating inflammasome-associated proteins may have utility as diagnostic biomarkers of neuroinflammatory conditions, including TBI. Finally, novel and promising areas of research will be highlighted, including the potential involvement of the NLRP3 inflammasome in mild TBI, how factors such as biological sex may affect NLRP3 activity in TBI, and the use of emerging biomarker platforms. Taken together, this review highlights the exciting potential of the NLRP3 inflammasome as a target for treatments and biomarkers that may ultimately be used to improve TBI management.

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“…31 They have also been implicated in both severe and mild forms of TBI. 32,33 Neurons can package ncRNAs within protective vesicles, allowing them to traverse the extracellular space, dock at distant cells, and influence gene expression. 34 Thus, measurement of salivary ncRNAs arising from the five cranial nerves in the oropharynx may provide a noninvasive molecular window into the physiology of mTBI.…”

Section: Introductionmentioning

confidence: 99%