The evolving role of extracellular vesicles (exosomes) as biomarkers in traumatic brain injury: Clinical perspectives and therapeutic implications

Abstract

Developing effective disease-modifying therapies for neurodegenerative diseases (NDs) requires reliable diagnostic, disease activity, and progression indicators. While desirable, identifying biomarkers for NDs can be difficult because of the complex cytoarchitecture of the brain and the distinct cell subsets seen in different parts of the central nervous system (CNS). Extracellular vesicles (EVs) are heterogeneous, cell-derived, membrane-bound vesicles involved in the intercellular communication and transport of cell-specific cargos, such as proteins, Ribonucleic acid (RNA), and lipids. The types of EVs include exosomes, microvesicles, and apoptotic bodies based on their size and origin of biogenesis. A growing body of evidence suggests that intercellular communication mediated through EVs is responsible for disseminating important proteins implicated in the progression of traumatic brain injury (TBI) and other NDs. Some studies showed that TBI is a risk factor for different NDs. In terms of therapeutic potential, EVs outperform the alternative synthetic drug delivery methods because they can transverse the blood–brain barrier (BBB) without inducing immunogenicity, impacting neuroinflammation, immunological responses, and prolonged bio-distribution. Furthermore, EV production varies across different cell types and represents intracellular processes. Moreover, proteomic markers, which can represent a variety of pathological processes, such as cellular damage or neuroinflammation, have been frequently studied in neurotrauma research. However, proteomic blood-based biomarkers have short half-lives as they are easily susceptible to degradation. EV-based biomarkers for TBI may represent the complex genetic and neurometabolic abnormalities that occur post-TBI. These biomarkers are not caught by proteomics, less susceptible to degradation and hence more reflective of these modifications (cellular damage and neuroinflammation). In the current narrative and comprehensive review, we sought to discuss the contemporary knowledge and better understanding the EV-based research in TBI, and thus its applications in modern medicine. These applications include the utilization of circulating EVs as biomarkers for diagnosis, developments of EV-based therapies, and managing their associated challenges and opportunities.

MSC microvesicles loaded G-quadruplex-enhanced circular single-stranded DNA-9 inhibits tumor growth by targeting MDSCs

“…In contrast to traditional drug carriers, such as liposomes, micelles, and polymeric nanoparticles, MVs as a natural drug carrier, can avoid phagocytosis and prolong the half-life of drugs in blood [ 21 , 22 ]. It releases drugs into the cytoplasm through cell membrane fusion and has good biocompatibility [ 23 ].…”

Cell Type-Specific Extracellular Vesicles and Their Impact on Health and Disease

“…EVs can pass through the blood–brain barrier, which can enable them to be engineered to deliver molecular tracers, thus potentially illuminating injured areas within the brain without the need for high-resolution scanning neurotechnology. EVs are also implicated with neuronal–glial cell communication and reduced neuroinflammation when derived from the neuronal cells of the CNS [ 140 ].…”

Review on the Role of Salivary Biomarkers in the Diagnosis of Mild Traumatic Brain Injury and Post-Concussion Syndrome

“…In this way, the plethora of molecular pathways that implicate the formation of extracellular vesicles are usually based on signal transduction modulation and cellular communication. In this way, exosomes, microvesicles, and apoptotic bodies are potent means of protein dissemination during TBI progression [ 62 ].…”

“…Moreover, EVs were shown to participate in the removal of unwanted active molecules (for example, in AD, EVs are thought to be one of the milieus through which the pathogenic proteins are spread) [ 63 , 64 ]. The possible roles of EVs in TBI were recently described by Khan et al [ 62 ], who mainly highlighted the clinical implications in the therapeutic perspectives of EVs. However, despite the fact that the difficulties in isolating EVs are surpassed by novel techniques [ 65 , 66 , 67 ], EVs’ implications in TBI remain a controverted and unsolved puzzle.…”