Traumatic brain injury (TBI) is widely acknowledged as a predominant public health issue, as it has the highest incidence rate among all common neurological disorders (Maas et al., 2022). Furthermore, TBI is distinguished by its persistent nature and links to chronic conditions, such as elevated risk of developing neurodegenerative disorders that manifest later in life, including Alzheimer's disease (Johnson et al., 2023; Yashkin et al., 2023), Vascular Dementia (Leung et al., 2022), and Amyotrophic Lateral Sclerosis (Iverson et al., 2023; Wiesner et al., 2018). These consequences create a substantial burden on the overall well-being of the population. In addition, due to increasing traffic volume and an aging demographic, TBI has emerged as a growing concern (Jiang et al., 2019a; Markovic et al., 2021).

After TBI, a series of neurological events unfold, including neuroinflammation, glial activation, neuronal death, white matter injury, cerebral edema, and disruption of the brain microvessels. This intricate sequence of events results in substantial shifts in the expression of both coding and non-coding genes (Sun et al., 2018b; Wu et al., 2022b). Hence, to solve this critical issue effectively, it is imperative to acquire a more comprehensive understanding of the alterations to gene expression induced by TBI and the underlying molecular regulatory processes.

Non-coding RNAs (ncRNAs), also described as the “dark matter” of DNA, refer to a specific kind of RNA molecule that cannot undergo translation into proteins (Arraiano, 2021). These ncRNAs can be categorized into two main groups: housekeeping ncRNAs, which consist of rRNAs and tRNAs, and regulatory ncRNAs, which mainly include microRNAs (miRNAs, miRs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) (Zong et al., 2023). Notably, regulatory ncRNAs have recently been the subject of intensive research across a variety of academic disciplines, such as cancer (Slack and Chinnaiyan, 2019; Toden et al., 2021), neurodevelopmental disorders (Ang et al., 2019; Ziats and Rennert, 2013), neurodegenerative diseases (Takousis et al., 2019; Zhou et al., 2022b), as well as central nervous system (CNS) injuries (Ma et al., 2020a; Sun et al., 2020; Zhang et al., 2019b, 2020a).

Notably, a substantial body of evidence demonstrates that regulatory ncRNAs not only participate in the initial damage caused by TBI but also play a pivotal role in the subsequent secondary injury process (Atif and Hicks, 2019; Mohamadzadeh et al., 2023; Sun et al., 2022). Furthermore, recent technological breakthroughs, notably next-generation sequencing (NGS), have significantly facilitated the discovery and characterization of regulatory ncRNAs after TBI (Ren et al., 2020; Zhong et al., 2016). Therefore, a deeper understanding of the changes in expression patterns of regulatory ncRNAs and its molecular mechanisms can potentially contribute to improvements in the diagnosis, treatment, and prognosis of TBI.

In this review, we will offer a complete summary of current studies on the functions and pathologic mechanisms of regulatory ncRNAs in TBI. Moreover, we will provide a concise overview of the potential applications of these regulatory ncRNAs in TBI from both clinical and experimental studies.