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Sphingolipids and microRNA Changes in Blood following Blast Traumatic Brain Injury: An Exploratory Study
Venkata Siva Sai Sujith Sajja1,2,3,4, Anna Jablonska1,2, Norman Haughey5,6
11 Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine , Baltimore, Maryland.
Abstract:
At present, accurate and reliable biomarkers to ascertain the presence, severity, or prognosis of blast traumatic brain injury (bTBI) are lacking. There is an urgent need to establish accurate and reliable biomarkers capable of mbTBI detection. Currently, there are no studies that identify changes in miRNA and lipids at varied severities of bTBI. Various biological components such as lipids, circulating mRNA, and miRNA, could potentially be detected using advanced techniques such as next-generation sequencing and mass spectroscopy. Therefore, plasma analysis is an attractive approach with which to diagnose and treat brain injuries. Subacute changes in plasma microRNA (miRNA) and lipid composition for sphingolipids were evaluated in a murine model of mild-to-moderate bTBI using next-generation sequencing and mass spectroscopy respectively. Animals were exposed at 17, 17 × 3, and 20 psi blast intensities using a calibrated blast simulator. Plasma lipid profiling demonstrated decreased C18 fatty acid chains of sphingomyelins and increased ceramide levels when compared with controls. Plasma levels of brain-enriched miRNA, miR-127 were increased in all groups while let-7a, b, and g were reduced in the 17 × 3 and 20 psi groups, but let 7d was increased in the 17 psi group. The majority of the miRs and lipids are highly conserved across different species, making them attractive to explore and potentially employ as diagnostic markers. It is tempting to speculate that sphingolipids, miR-128, and the let-7 family could predict mTBI, while a combination of miR-484, miR-122, miR-148a, miR-130a, and miR-223 could be used to predict the overall status of injury following blast injury.
Insights
Researchers identified specific microRNAs (miRNAs) and lipids in plasma that change after blast traumatic brain injury (bTBI) in mice. These biomarkers could help detect and assess the severity of bTBI.
Area of Science:
- Neuroscience
- Biochemistry
- Genomics
Background:
- Accurate biomarkers for blast traumatic brain injury (bTBI) are currently lacking.
- There is an urgent need for reliable methods to detect and assess bTBI severity.
- Previous studies have not investigated changes in miRNA and lipids at varied bTBI severities.
Purpose of the Study:
- To evaluate subacute changes in plasma microRNA (miRNA) and sphingolipid composition in a murine model of mild-to-moderate bTBI.
- To identify potential plasma biomarkers for bTBI detection and severity assessment.
Main Methods:
- A murine model was used, exposing animals to controlled blast intensities (17, 17x3, and 20 psi).
- Plasma lipid profiling was performed using mass spectroscopy.
- Plasma miRNA levels were analyzed using next-generation sequencing.
Main Results:
- Decreased C18 fatty acid chains of sphingomyelins and increased ceramide levels were observed in plasma.
- Brain-enriched miR-127 levels increased in all blast groups.
- Specific let-7 family miRNAs showed altered expression patterns correlating with blast intensity.
Conclusions:
- Plasma sphingolipids and specific miRNAs (let-7 family, miR-128) show potential as biomarkers for mild-to-moderate bTBI.
- Combinations of miRNAs (e.g., miR-484, miR-122) may help predict overall injury status.
- These conserved biomarkers warrant further investigation for clinical application in diagnosing and managing bTBI.
