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MicroRNAs as Brain Injury Biomarker

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General Methods in Biomarker Research and their Applications

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Abstract

MicroRNAs (miRNAs) are small, noncoding endogenous RNA regulatory molecules, which modulate gene expression either by mRNA degradation or translation suppression. MiRNAs in serum are resistant to repeated freeze thaw, enzymatic degradation and can survive extreme pH conditions. Due to these properties, miRNAs have the advantage over protein-based biomarkers and have recently emerged as novel biomarkers for many diseases and disorders. Worldwide, brain injuries caused by traumatic brain injury (TBI), cerebral ischemia, and stroke are the leading causes of death and disability. TBI is classified as mild, moderate, or severe depending on the severity and the cause of injury to the brain. Cerebral ischemia can be further classified as global or focal. Stroke is caused by obstruction of blood flow in brain vessels and its disruption leads to hemorrhage. Mild brain injuries such as mild TBI and mild ischemic insults can often go undiagnosed and untreated due to the lack of immediate visible symptoms. Current diagnostic techniques including imaging are not capable of detecting low-level trauma to the brain. Recent studies on unique changes in expression of miRNAs in serum and brain samples after TBI or stroke show great promise of developing them as noninvasive test for brain injury. In this chapter, the recent progress of miRNAs in brain injuries has been reviewed especially for their utility as biomarker. The various methods that are currently being followed for identifying the altered expression of miRNAs in brain injuries and their analysis has also been discussed. In addition to the diagnostic and prognostic biomarkers, the brain injury-altered miRNAs have the potential to be used in therapeutics and are discussed with special emphasis on TBI and cerebral ischemia.

Authors Disclosure Statement

The opinions expressed here are those of the authors and should not be construed as official or reflecting the views of the Uniformed Services University of Health Sciences, Bethesda, Maryland, and the Birla Institute of Technology and Science, Pilani, Rajasthan, India. No competing financial interests exist.

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Abbreviations

Ago2:

Argonaut2

AMPAR:

α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor

AUC:

Area Under the Curve

BACE-1:

Beta-Site APP-Cleaving Enzyme -1

BBB:

Blood-Brain Barrier

BIP:

Binding Immunoglobulin Protein

BOP:

Blast Overpressure

CCI:

Controlled Cortical Impact

cDNA:

Complimentary DNA

CNS:

Central Nervous System

CSF:

Cerebrospinal Fluid

CSF-MP:

CSF-Microparticle

CT:

Computed Tomography

DIANA:

DNA Intelligence Analysis

DNA:

Deoxyribonucleic Acid

DTI:

Diffusion Tensor Imaging

FDG-PET:

Fluorodeoxyglucose Positron Emission Tomography

FGFR:

Fibroblast Growth Factor Receptor

fMRI:

Functional Magnetic Resonance Imaging

GCS:

Glasgow Coma Scale

GDP:

Gross Domestic Product

GFAP:

Glial Fibrillary Acidic Protein

GO:

Gene Ontology

GRN:

Granulin

GRP78:

Glucose-Regulated Protein, 78 kDa

GSEA:

Gene Set Enrichment Analysis

HSP:

Heat Shock Protein

ICV:

Intracerebroventricular

IPA:

Ingenuity Pathway Analysis

LNA:

Locked Nucleic Acid

LOWESS:

Locally Weighted Regression

MAMI:

MetA Mir: Target Interference

MCAO:

Middle Cerebral Artery Occlusion

MGB:

Minor Groove Binding

miRNA:

MicroRNA

MRI:

Magnetic Resonance Imaging

mTBI:

Mild TBI

NGS:

Next-Generation Sequencing

NMDA:

N-Methyl-d-Aspartate

NR2B:

N-Methyl d-Aspartate Receptor Subtype 2B

NSC:

Neural Stem Cells

NTERA:

Neuronally Committed Human Teratocarcinoma Cell Line

PBMC:

Peripheral Blood Mononuclear Cells

PTA:

Posttraumatic Amnesia

RIN:

RNA Integrity Number

RISC:

RNA-Induced Silencing Complex

RNA:

Ribonucleic Acid

RNA-seq:

Deep Sequencing of Small RNA Libraries

ROC:

Receiver Operating Characteristic

RT-qPCR:

Real-Time Quantitative Polymerase Chain Reaction

snRNA:

Small Nucleolar RNA

SPECT:

Single-Photon Emission Computed Tomography

TBI:

Traumatic Brain Injury

Tm:

Melting Temperature

TRBP:

TAR RNA-Binding Protein

UCH-L1:

Ubiquitin Carboxyl-Terminal Esterase L1

WHO:

World Health Organization

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Acknowledgements

This work was supported by a grant from the Defense Medical Research and Development Program to Dr. Radha K. Mahaeshwari.

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Authors and Affiliations

  1. Department of Pathology, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, 4301, Jones Bridge Road, Bethesda, MD, 20814-4799, USA

    Nagaraja S. Balakathiresan, Manish Bhomia, Paridhi Gupta, Raghavendar Chandran, Anuj Sharma & Radha K. Maheshwari

  2. Biological Sciences Group, Birla Institute of Technology and Science, Pilani, Rajasthan, India

    Raghavendar Chandran

Authors
  1. Nagaraja S. Balakathiresan
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  2. Manish Bhomia
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  3. Paridhi Gupta
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  4. Raghavendar Chandran
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  5. Anuj Sharma
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  6. Radha K. Maheshwari
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Corresponding author

Correspondence to Radha K. Maheshwari .

Editor information

Editors and Affiliations

  1. Diabetes & Nutritional Sciences Division, King's College, London, United Kingdom

    Victor R. Preedy

  2. Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, United Kingdom

    Vinood B. Patel

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Balakathiresan, N.S., Bhomia, M., Gupta, P., Chandran, R., Sharma, A., Maheshwari, R.K. (2014). MicroRNAs as Brain Injury Biomarker. In: Preedy, V., Patel, V. (eds) General Methods in Biomarker Research and their Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7740-8_6-1

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  • DOI: https://doi.org/10.1007/978-94-007-7740-8_6-1

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  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-7740-8

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

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