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Updated: Dec 27, 2025
Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury
Published on: August 14, 2019
MicroRNA sequencing of rat hippocampus and human biofluids identifies acute, chronic, focal and diffuse traumatic
Harris A Weisz1, Deborah Kennedy1, Steven Widen1
1The University of Texas Medical Branch at Galveston, Galveston, TX, USA.
Abstract:
High-throughput sequencing technologies could improve diagnosis and classification of TBI subgroups. Because recent studies showed that circulating microRNAs (miRNAs) may serve as noninvasive markers of TBI, we performed miRNA-seq to study TBI-induced changes in rat hippocampal miRNAs up to one year post-injury. We used miRNA PCR arrays to interrogate differences in serum miRNAs using two rat models of TBI (controlled cortical impact [CCI] and fluid percussion injury [FPI]). The translational potential of our results was evaluated by miRNA-seq analysis of human control and TBI (acute and chronic) serum samples. Bioinformatic analyses were performed using Ingenuity Pathway Analysis, miRDB, and Qlucore Omics Explorer. Rat miRNA profiles identified TBI across all acute and chronic intervals. Rat CCI and FPI displayed distinct serum miRNA profiles. Human miRNA profiles identified TBI across all acute and chronic time points and, at 24 hours, discriminated between focal and diffuse injuries. In both species, predicted gene targets of differentially expressed miRNAs are involved in neuroplasticity, immune function and neurorestoration. Chronically dysregulated miRNAs (miR-451a, miR-30d-5p, miR-145-5p, miR-204-5p) are linked to psychiatric and neurodegenerative disorders. These data suggest that circulating miRNAs in biofluids can be used as "molecular fingerprints" to identify acute, chronic, focal or diffuse TBI and potentially, presence of neurodegenerative sequelae.
Insights
Circulating microRNAs (miRNAs) serve as molecular fingerprints for traumatic brain injury (TBI). This study identifies specific miRNAs in rats and humans, distinguishing acute, chronic, and focal TBI, and predicting neurodegenerative risks.
Area of Science:
- Neuroscience
- Genomics
- Biomarker Discovery
Background:
- Traumatic brain injury (TBI) diagnosis and classification can be improved by high-throughput sequencing.
- Circulating microRNAs (miRNAs) show promise as noninvasive biomarkers for TBI.
Purpose of the Study:
- To investigate TBI-induced changes in rat hippocampal and serum miRNAs up to one year post-injury.
- To evaluate the translational potential of serum miRNAs as TBI biomarkers in humans.
- To identify specific miRNA profiles associated with different TBI types and time points.
Main Methods:
- miRNA sequencing (miRNA-seq) and miRNA PCR arrays were used in rat models (CCI and FPI) and human serum samples (acute and chronic TBI).
- Bioinformatic analyses included Ingenuity Pathway Analysis, miRDB, and Qlucore Omics Explorer.
- Gene targets of differentially expressed miRNAs were predicted.
Main Results:
- Rat miRNA profiles detected TBI across acute and chronic intervals, with distinct profiles for CCI and FPI models.
- Human miRNA profiles identified TBI across all time points and differentiated focal from diffuse injuries at 24 hours.
- Predicted gene targets are involved in neuroplasticity, immune function, and neurorestoration.
- Chronically dysregulated miRNAs are linked to psychiatric and neurodegenerative disorders.
Conclusions:
- Circulating miRNAs can serve as "molecular fingerprints" for identifying acute, chronic, focal, or diffuse TBI.
- Serum miRNA profiles may predict the presence of neurodegenerative sequelae following TBI.
- miRNA-seq offers a powerful tool for TBI biomarker discovery and classification.
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