Co-Expression Network Analysis of MicroRNAs and Proteins in Severe Traumatic Brain Injury: A Systematic Review

Abstract

Traumatic brain injury (TBI) represents one of the leading causes of mortality and morbidity worldwide, placing an enormous socioeconomic burden on healthcare services and communities around the world. Survivors of TBI can experience complications ranging from temporary neurological and psychosocial problems to long-term, severe disability and neurodegenerative disease. The current lack of therapeutic agents able to mitigate the effects of secondary brain injury highlights the urgent need for novel target discovery. This study comprises two independent systematic reviews, investigating both microRNA (miRNA) and proteomic expression in rat models of severe TBI (sTBI). The results were combined to perform integrated miRNA-protein co-expression analyses with the aim of uncovering the potential roles of miRNAs in sTBI and to ultimately identify new targets for therapy. Thirty-four studies were included in total. Bioinformatic analysis was performed to identify any miRNA–protein associations. Endocytosis and TNF signalling pathways were highlighted as common pathways involving both miRNAs and proteins found to be differentially expressed in rat brain tissue following sTBI, suggesting efforts to find novel therapeutic targets that should be focused here. Further high-quality investigations are required to ascertain the involvement of these pathways and their miRNAs in the pathogenesis of TBI and other CNS diseases and to therefore uncover those targets with the greatest therapeutic potential.

Role of statins in regulating molecular pathways following traumatic brain injury: A system pharmacology study

“…TBI affects over 2.5 million people in the USA and Europe and leads to serious disability in around 40 % of involved patients [16]. Previous studies supported the role of various protein and gene dysregulation in brain sensitivity and recovery in TBI diseases [19,63,64]. Statins in numerous investigations displayed a role in ameliorating post-TBI implications.…”

Traumatic Brain Injury Leads to Alterations in Contusional Cortical miRNAs Involved in Dementia

“…Although there are numerous reports investigating the alterations of miRNAs following TBI, these studies were mostly performed in blood or CSF as potential biomarkers [ 26 , 37 ]. The studies carried out in brains of animal models of TBI have revealed different patterns, depending on the time post-injury, the brain region investigated, the model used, and the severity of the injury [ 23 , 38 , 39 , 40 , 41 ]. For instance, one of the first reports carrying out miRNA studies in animal models of TBI reported altered expression levels of miR-107, -130a, -223, -292-5p, -433-3p, -451, -541, and -711 immediately post-injury [ 42 ].…”

“…Studies performed 2 weeks post-injury are scarce [ 43 ] and do not involve the analysis of the pericontusional tissue. A recent meta-analysis of 34 studies performed in severe TBI models revealed that the most common pathways regulated after TBI by miRNAs involve the TNFα and endocytosis signalling [ 41 ]. Interestingly, the list of miRNAs involved included miR-107 and miR-181b, which were also found altered in our study.…”

Study on serum miR-185-5p in assessing the injury severity and prognosis of patients with traumatic brain injury

“…miRNAs also play a crucial role in various physiological and pathological processes such as cell growth, differentiation, metabolism, apoptosis, angiogenesis, and tumorigenesis. miRNAs play an essential role in maintaining and regulating physiological functions in various diseases, including TBI, and therefore are receiving increasing attention in disease diagnosis and treatment targets [20] [21] [22] . miR-425-5p, miR-16, miR-92a, and miR-765 are abnormally expressed in patients with TBI and have high diagnostic values [23] .…”