Journal
BRAIN INJURY
Volume 31, Issue 1, Pages 106-119Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/02699052.2016.1213420
Keywords
Mild traumatic brain injury; brain; microRNA (miRNA); weight-drop injury; closed head injury
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Funding
- Defense Medical Research and Development Program (DMRDP)
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Objective: To investigate the effect of heterogeneity in mTBI on miRNA expression in mouse brain and to identify molecular pathways targeted' by the modulated miRNAs. Methods: A weight drop device was used to induce four, increasing grades of mTBI. MiRNA expression was evaluated using TaqMan rodent miRNA arrays. Bioinformatics analysis was done using the DIANA miRPath tool and Ingenuity Pathway Analysis software. Histology of brain sections was evaluated using H&E staining. Results: No histologic lesions were observed in the brains of injured mice; however, significant modulation in miRNA expression profile was observed. Global miRNA profiling, indicated a trend Of decrease in the number of modulated' miRNAs from 24 hours to day 7 post-injury, except for the most severe grade of mTBI. Canonical pathways like calcium signalling, synaptic pathways and axon guidance pathway were the major targets of the modulated miRNAs. Network correlation analyses indicated an interaction between the modulated miRNAs and putative protein biomarkers of TBI. Conclusions: The data demonstrated that varying intensities of mTBI induced a differential miRNA expression profile in the brain post-injury. Pathways such as calcium and synaptic signalling, were major targets of modulated miRNAs and may play a role in the pathophysiology of mTBI.
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