Traumatic brain injury (TBI) is damage to the brain caused by an external force (Stocchetti et al., 2017). The major causes of TBI include falls, car accidents, and violence. Among children and adolescents worldwide, TBI is the leading cause of death and disability. Males suffer from TBI approximately twice as often as females (Capizzi et al., 2020). Symptoms of mild TBI are highly variable and, in addition to the loss of consciousness, may include nausea, vomiting, dizziness, and headache, but also cognitive symptoms (such as poor concentration and memory problems) and behavioral symptoms (such as irritability and emotional instability) (Khellaf et al., 2019).

miR-9a-5p is a non-coding RNA that is found in large amounts in the central nervous system. Under normal conditions, it is involved in axon extension, dendrite growth, neuronal synapse development, neural progenitor cell differentiation, neurogenesis, and angiogenesis (Cao et al., 2020). miR-9a-5p has been reported to alleviate ventilator-induced lung injury in rats by down-regulating CXCR4 expression and inhibiting activation of the MAPK signaling pathway (Lei et al., 2022). In addition, miR-9a-5p is involved in ischemic injury by targeting KLF5 to promote cardiomyocyte apoptosis (Yang et al., 2019). miR-9a-5p can regulate hepatic stellate by inhibiting Sirt1 and thus cell proliferation and migration in response to stress (Qi et al., 2015). Also, miR-9a-5p has been linked to ischemic brain damage, and researchers have found that in rats with focal cerebral ischemia, miR-9a-5p reduces ischemic damage by focusing on atg5-mediated autophagy (Wu et al., 2018). Overexpression of miR-9a-5p reduces the damage caused by the NLRP1 inflammasome after ischemic stroke in rats (Cao et al., 2020). Meanwhile, evidence has shown that miR-9-5p is closely related to TBI, and down-regulation of miR-9-5p increased the release of astrocyte-derived neurotrophic factor by promoting astrocyte proliferation around TBI. The effect of miR-9-5p on TBI is to promote neurological recovery and thus improve TBI (Wu et al., 2021).

ELAVL1 contains 3 RNA binding domains, and its main biological function is to regulate gene expression by stabilizing mRNA (Seo et al., 2022). ELAVL1 has multiple biological functions. ELAVL1 is involved in the regulation of cellular iron death, ischemia/reperfusion injury, and tumorigenesis and development. In addition, ELAVL1 is associated with the development of ischemic injury. A previous study has reported that ELAVL1 transcriptional activation by FOXC1 promotes iron death in myocardial ischemia/reperfusion injury through the regulation of autophagy, leading to myocardial injury (Xu et al., 2021). Furthermore, ELAVL1 interacts with other m6A regulators to promote prostate cancer progression (Cai et al., 2022). ELAVL1 also regulates hepatitis B virus replication and hepatocellular carcinoma cell growth (Kanzaki et al., 2022). Finally, the association between ELAVL1 and the onset of brain injury has been established. The downregulation of ELAVL1 enhances cellular viability by reducing DNMT3B-dependent PINK1 methylation, thereby alleviating neuronal injury induced by iron-induced cell death in a rat model of cerebral ischemia/reperfusion (Du et al., 2022). ELAVL1 has been identified as a potential therapeutic target to prevent cell death after TBI (White et al., 2016). Still, the exact molecular mechanism still needs to be clarified.

Vascular endothelial growth factor (VEGF) is a signaling protein many cells produce that stimulates blood vessel formation (Senger et al., 1983). VEGF can restore oxygen supply to tissues when inadequate blood circulation, for example, under hypoxic conditions (Palmer and Clegg, 2014). VEGF starts the growth of new blood vessels during embryonic development. It also encourages the growth of new blood vessels after an injury (Apte et al., 2019). In addition, studies have reported an association between VEGF and the occurrence of TBI. It has been found that after a TBI, the expression of VEGF and MMP-9 goes up. This contributes to the breaking down of the blood-brain barrier and neurological damage (Wei et al., 2022). Inhibition of VEGF activity reduces brain edema in pathological states, thereby improving TBI (Zhou et al., 2020).

This study investigated miR-9a-5p targeting and regulating ELAVL1/VEGF signaling pathway to regulate brain tissue injury in TBI rats. We initially concluded that miR-9a-5p reduced brain tissue injury in TBI rats by targeting and inhibiting ELAVL1 and down-regulating VEGF expression. It also makes miR-9a-5p, ELAVL1, VEGF, and other factors a target for brain tissue injury treatment, thus providing a new theoretical basis for diagnosing and treating tissue injury.