Extracellular Vesicle Proteins and MicroRNAs as Biomarkers for Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a heterogeneous condition, associated with diverse etiologies, clinical presentations and degrees of severity, and may result in chronic neurobehavioral sequelae. The field of TBI biomarkers is rapidly evolving to address the many facets of TBI pathology and improve its clinical management. Recent years have witnessed a marked increase in the number of publications and interest in the role of extracellular vesicles (EVs), which include exosomes, cell signaling, immune responses, and as biomarkers in a number of pathologies. Exosomes have a well-defined lipid bilayer with surface markers that reflect the cell of origin and an aqueous core that contains a variety of biological material including proteins (e.g., cytokines and growth factors) and nucleic acids (e.g., microRNAs). The presence of proteins associated with neurodegenerative changes such as amyloid-β, α-synuclein and phosphorylated tau in exosomes suggests a role in the initiation and propagation of neurological diseases. However, mechanisms of cell communication involving exosomes in the brain and their role in TBI pathology are poorly understood. Exosomes are promising TBI biomarkers as they can cross the blood-brain barrier and can be isolated from peripheral fluids, including serum, saliva, sweat, and urine. Exosomal content is protected from enzymatic degradation by exosome membranes and reflects the internal environment of their cell of origin, offering insights into tissue-specific pathological processes. Challenges in the clinical use of exosomal cargo as biomarkers include difficulty in isolating pure exosomes, variable yields of the isolation processes, quantification of vesicles, and lack of specificity of exosomal markers. Moreover, there is no consensus regarding nomenclature and characteristics of EV subtypes. In this review, we discuss current technical limitations and challenges of using exosomes and other EVs as blood-based biomarkers, highlighting their potential as diagnostic and prognostic tools in TBI.

Challenges in Biomaterial-Based Drug Delivery Approach for the Treatment of Neurodegenerative Diseases: Opportunities for Extracellular Vesicles

“…The use of EVs as diagnostic biomarkers also promises to fill the diagnostic accuracy gap in many different diseases, such as in TBI [ 134 ]. A recent study used miRNA EVs and GluR2 + EVs to identify TBI presence, severity, recovery, and history of prior injuries [ 135 ].…”

“…A recent study used miRNA EVs and GluR2 + EVs to identify TBI presence, severity, recovery, and history of prior injuries [ 135 ]. Moreover, AD biomarkers, such as Aβ and P-tau concentrations, were higher in EVs that were isolated from TBI patients than from controls [ 134 , 136 ]. Additionally, EV-tau and Aβ42 were higher in patients with a history of multiple TBIs.…”

“…Additionally, EV-tau and Aβ42 were higher in patients with a history of multiple TBIs. Furthermore, EV neurofilament neuropolypeptide and glial fibrillary acidic protein were associated with TBI diffusion and recovery [ 134 ]. Unresolved or dysregulated immune responses after TBI can contribute to chronic activation of neurotoxic microglia, eventually leading to progressive neuronal cell death [ 137 ].…”

MicroRNAs at the Crossroad of the Dichotomic Pathway Cell Death vs. Stemness in Neural Somatic and Cancer Stem Cells: Implications and Therapeutic Strategies

“…It exceeds the purpose of this paper to describe the functions and potential applications of the numerous miRNAs in terms of diagnostic biomarkers since comprehensive reviews have been already written for AD [ 26 , 27 , 28 ] and PD [ 29 , 30 , 31 ], amyotrophic lateral sclerosis (ALS) [ 29 , 30 , 31 , 32 ], multiple sclerosis (MS) [ 33 , 34 ], traumatic brain injury (TBI) [ 35 , 36 ], or development-related syndromes, such as autism spectrum disorder (ASD) [ 37 , 38 ]. Instead, both in the central nervous system (CNS) and in the cerebral spinal fluid (CSF), miRNAs recruitment has boosted a novel impulse for the prognosis but, more strikingly, for neural regenerative medicine, shedding light on feasible translational brain applications that fill the present gap of clinical interventions represented by NSC transplantation.…”

Хронічна Посттравматична Енцефалопатія. Погляд На Проблему

“…Наявність в екзосомах білків, пов'язаних з нейродегенеративними змінами, такими, як амілоїд-β, α-синуклеїн та фосфорильований тау, вказує на їх роль в ініціюванні та розпо- всюдженні патології. Екзосоми можуть перетинати гематоенцефалічний бар'єр та бути виділені з периферичних рідин (сироватки, слини, сечі) [41]. Однак механізми клітинної комунікації із залученням екзосом у мозку та їх роль у патології недостатньо вивчені.…”