Identification of Serum MicroRNA Signatures for Diagnosis of Mild Traumatic Brain Injury in a Closed Head Injury Model

Sharma, Anuj; Chandran, Raghavendar; Barry, Erin S.; Bhomia, Manish; Hutchison, Mary Anne; Balakathiresan, Nagaraja S.; Grunberg, Neil E.; Maheshwari, Radha K.

doi:10.1371/journal.pone.0112019

Cited by 47 publications

(50 citation statements)

References 96 publications

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“…Of these, miR-99b-5p has been shown to be increased in circulation in mice 3 h after induction of mild traumatic brain injury (Sharma et al, 2014). However, in another study assessing serum microRNAs following a very different type and intensity of stress (3 days of immobilization and tail shock), a set of microRNAs distinct from those identified here were differentially expressed two weeks after stress .…”

Section: Discussionmentioning

confidence: 54%

MicroRNAs as biomarkers of resilience or vulnerability to stress

et al. 2015

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Identifying novel biomarkers of resilience or vulnerability to stress could provide valuable information for the prevention and treatment of stress-related psychiatric disorders. To investigate the utility of blood microRNAs as biomarkers of resilience or vulnerability to stress, microRNAs were assessed before and after 7days of chronic social defeat in rats. Additionally, microRNA profiles of two important stress-regulatory brain regions, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA), were assessed. Rats that displayed vulnerability to subsequent chronic stress exhibited reductions in circulating miR-24-2-5p, miR-27a-3p, miR-30e-5p, miR-3590-3p, miR-362-3p, and miR-532-5p levels. In contrast, rats that became resilient to stress displayed reduced levels of miR-139-5p, miR-28-3p, miR-326-3p, and miR-99b-5p compared to controls. In the mPFC, miR-126a-3p and miR-708-5p levels were higher in vulnerability compared to resilient rats. In the BLA, 77 microRNAs were significantly altered by stress but none were significantly different between resilient and vulnerable animals. These results provide proof-of-principle that assessment of circulating microRNAs is useful in identifying individuals who are vulnerable to the effects of future stress or individuals who have become resilient to the effects of stress. Furthermore, these data suggest that microRNAs in the mPFC but not in the BLA are regulators of resilience/vulnerability to stress.

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Section: Discussionmentioning

confidence: 54%

MicroRNAs as biomarkers of resilience or vulnerability to stress

et al. 2015

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“…Plasma levels of miR-16 and miR-92a were shown to be elevated in humans following mild or severe TBI compared to controls (Redell et al, 2010). In mice, serum miRNA profiles were shown to be altered as early as 3h following a mild closed head injury compared to controls regardless of the severity of mild injury (Sharma et al, 2014). In adult rats, levels of let-7i were shown to be increased in both serum and CSF as early as 3h following blast TBI (Balakathiresan et al, 2012).…”

Section: Micrornas As Tbi and Sci Biomarkersmentioning

confidence: 99%

Non-coding RNAs and neuroprotection after acute CNS injuries

Chandran

Mehta

2017

Neurochemistry International

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Accumulating evidence indicates that various classes of non-coding RNAs (ncRNAs) including microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs) and long non-coding RNAs (lncRNAs) play important roles in normal state as well as the diseases of the CNS. Interestingly, ncRNAs have been shown to interact with messenger RNA, DNA and proteins, and these interactions could induce epigenetic modifications and control transcription and translation, thereby adding a new layer of genomic regulation. The ncRNA expression profiles are known to be altered after acute CNS injuries including stroke, traumatic brain injury and spinal cord injury that are major contributors of morbidity and mortality worldwide. Hence, a better understanding of the functional significance of ncRNAs following CNS injuries could help in developing potential therapeutic strategies to minimize the neuronal damage in those conditions. The potential of ncRNAs in blood and CSF as biomarkers for diagnosis and/or prognosis of acute CNS injuries has also gained importance in the recent years. This review highlighted the current progress in the understanding of the role of ncRNAs in initiation and progression of secondary neuronal damage and their application as biomarkers after acute CNS injuries.

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“…Sharma et al (2014) used a weight drop model and reported increasing mNSS-R scores with increased weight and height when mice were evaluated 1 day postinjury. Interestingly, in the same study, these investigators were unable to find an injury effect using a previous version of the NSS.…”

Section: Anticipated Resultsmentioning

confidence: 99%

The Revised Neurobehavioral Severity Scale (NSS‐R) for Rodents

et al. 2016

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Motor and sensory deficits are common following traumatic brain injury (TBI). Although rodent models provide valuable insight into the biological and functional outcomes of TBI, the success of translational research is critically dependent upon proper selection of sensitive, reliable, and reproducible assessments. Published literature includes various observational scales designed to evaluate post-injury functionality; however, the heterogeneity in TBI location, severity, and symptomology can complicate behavioral assessments. The importance of choosing behavioral outcomes that can be reliably and objectively quantified in an efficient manner is becoming increasingly important. The Revised Neurobehavioral Severity Scale (NSS-R) is a continuous series of specific, sensitive, and standardized observational tests that evaluate balance, motor coordination, and sensorimotor reflexes in rodents. The tasks follow a specific order designed to minimize interference: balance, landing, tail raise, dragging, righting reflex, ear reflex, eye reflex, sound reflex, tail pinch, and hindpaw pinch. The NSS-R has proven to be a reliable method differentiating brain-injured rodents from non-brain-injured rodents across many brain injury models.

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Identification of Serum MicroRNA Signatures for Diagnosis of Mild Traumatic Brain Injury in a Closed Head Injury Model

Cited by 47 publications

References 96 publications

MicroRNAs as biomarkers of resilience or vulnerability to stress

MicroRNAs as biomarkers of resilience or vulnerability to stress

Non-coding RNAs and neuroprotection after acute CNS injuries

The Revised Neurobehavioral Severity Scale (NSS‐R) for Rodents

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