An Overview on the Use of miRNAs as Possible Forensic Biomarkers for the Diagnosis of Traumatic Brain Injury

Abstract

Determining the cause of death is one of the main goals of forensic pathology. However, conditions can occur in which common approaches—external inspection, autopsy, histology, etc.—might not be conclusive. With the advancement of molecular biology, several investigative techniques have been developed over the years, and the application as approaches complementary to routine procedures has proved useful in these cases. In this context, microRNA (miRNA) profiling has attracted increasing interest due to these molecules’ ability to regulate physiological and pathological processes. The evidence of differential miRNA expression in both animal models and human samples of traumatic brain injury (TBI) has laid the basis for comprehension of the underlying pathophysiological mechanisms, thus allowing us to identify some of them as possible TBI diagnostic biomarkers. The present narrative review aims to explore the primary miRNAs involved in the mechanisms underlying TBI, which could be considered for future evaluation as possible markers in a post mortem setting.

Evaluation of a Set of miRNAs in 26 Cases of Fatal Traumatic Brain Injuries

“…In addition, the coup area and the surrounding areas show increased levels of these miRNAs. Although further experiments are needed to clarify the reasons for this finding, the alteration of these miRNAs in a large area of the brain agrees with the ability of miRNA molecules to be translocated into the extracellular department [ 10 , 14 ]. Nevertheless, diffusion from necrotic tissue is also likely [ 10 , 24 ].…”

“…In TBI, miRNAs are primarily studied in the plasma/serum of patients to assess the trauma’s severity for clinical purposes [ 10 ]. In contrast, there is a lack of data on miRNA levels within the brain tissues of deceased subjects [ 10 , 12 , 13 ].…”

“…In TBI, miRNAs are primarily studied in the plasma/serum of patients to assess the trauma’s severity for clinical purposes [ 10 ]. In contrast, there is a lack of data on miRNA levels within the brain tissues of deceased subjects [ 10 , 12 , 13 ]. In this study, after a pre-evaluation of seven miRNAs, the expression levels of three miRNAs were investigated in a set of injured human brains.…”

“…In recent years, RNA-based biomarkers, mostly miRNAs, have been proposed as valuable tools for investigating the cause of death [ 6 , 7 ], the post-mortem interval [ 8 ], and other topics [ 9 ] in forensic medicine [ 10 ]. However, the traumatic mechanisms and consequences for the brain are not fully understood at the molecular level.…”

“…Nevertheless, most studies focused on murine and rat models for which FFPE (formalin-fixed and paraffin-embedded) brain tissues tissue were easily available [ 15 , 16 , 17 ]. For humans, miRNAs associated with TBI were instead evaluated mainly in fluids such as peripheral blood, saliva, or cerebrospinal fluid [ 10 , 18 ].…”