Traumatic brain injury (TBI) is an insult to the brain from the application of external physical force that leads to temporary or permanent structural and functional impairment of the brain. TBI is a leading cause of injury-related death and disability 
. Around 1.7 million people sustain a TBI in the U.S. annually and 53,000 of them die from TBI-related injuries 
. In TBI survivors, neuropsychiatric abnormalities, such as cognitive deficits, emotional and behavioral problems are common and contribute substantially to post-TBI disabilities 
. The hippocampus is an essential brain region for cognition and emotion 
, and is vulnerable to TBI. TBI-related hippocampal damages, such as cell loss, disturbed neural circuits and impaired synaptic transmission and synaptic plasticity, are major pathophysiological changes in TBI 
, and are expected to lead to neuropsychiatric symptoms. However, the molecular and cellular mechanisms responsible for hippocampal damage and recovery following TBI are poorly understood. The structural and functional modification of the brain entails gene expression changes. In fact, studies in both humans and animal models of TBI show that gene expression is altered by TBI in multiple brain regions 
, but the molecular mechanisms underlying TBI-induced gene expression changes are unclear.
MicroRNAs (miRNAs) are a class of small non-coding RNAs which repress gene expression at the post-transcriptional level by translational inhibition and/or promoting mRNA degradation through binding of the miRNA seed regions (usually nucleotides 2–8 at the 5′ end) to their binding sites in the 3′ untranslated region (3′ UTR) of the target mRNAs 
. Each miRNA can potentially target up to hundreds of protein-coding transcripts due to imperfect base pairing between miRNAs and their targets. Hence, miRNAs exert pleiotropic effects on gene expression and regulate diverse biological processes, such as cell proliferation and differentiation and apoptosis 
. Over 1000 miRNAs have been identified in mammals and hundreds of them are expressed in the brain 
. miRNAs are crucial for proper brain functions. Loss of miRNAs in mice due to deficient expression of Dicer and DGCR8, which are two miRNA processing molecules, causes changes in synaptic protein expression, synaptic transmission, dendritic spine morphology, learning and memory 
. It has been reported that TBI alters miRNA expression in the hippocampus 
. Because changed miRNA expression is predicted to influence their target mRNA expression, it is possible that miRNAs play a role in regulating gene expression in TBI. Hence, a comprehensive analysis of miRNA expression profiles and identification of miRNAs modulated in TBI are essential to construct the signaling network responsible for TBI-induced gene expression changes.
Animal models are important tools for studying TBI. The lateral fluid percussion injury (FPI) model and the controlled cortical impact injury (CCI) model are two widely used animal models of focal TBI. FPI is delivered through a pressurized pulse of saline solution created by a piston 
. CCI is produced by a rigid impactor which delivers a mechanical energy to the intact dura. The parameters of CCI, such as impact velocity and depth, can be fine-tuned by adjusting the settings of the impactor, allowing injury severity to be precisely controlled 
Here, by employing the next generation sequencing platform, we analyze the miRNA transcriptomes in the rat hippocampus at 24 hours and 7 days after TBI in the CCI model. Deep sequencing provides superb sensitivity, quantifiability and throughput over microarray and quantitative RT-PCR assays for miRNAs. We show that distinct miRNAs are up- or down-regulated at the two post-CCI time points. To decipher the biological implication of altered miRNA expression, we design a miRNA-gene-GO enrichment analysis to identify biological functions that are regulated by the target genes of changed miRNAs. We find that different gene ontology (GO) terms are targeted by the miRNAs altered in expression at the early and late phase of TBI. Intriguingly, the biological processes associated with these GO terms are consistent with the characteristic post-CCI pathological, physiological and structural changes. These findings indicate that miRNA expression profile changes are a distinctive molecular signature of post-TBI brains, and regulation of gene expression by miRNAs might be an important component of the cellular programs used by the injured brain to modulate gene expression for management and repair of injury-related cell damages.