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

Article Immunology

Extracellular vesicle-associated cytokines in sport-related concussion

Timothy B. Meier et al.

Summary: The study reveals that EV-associated cytokines are significantly increased following acute concussion and may serve as potential biomarkers for concussion.

BRAIN BEHAVIOR AND IMMUNITY (2022)

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Review Critical Care Medicine

Can serum biomarkers be used to rule out significant intracranial pathology in emergency department patients with mild traumatic brain injury? A Systemic Review & Meta-Analysis

Alice Rogan et al.

Summary: This study aimed to assess the use of serum and plasma biomarkers to exclude significant intracranial injuries in TBI patients and found that S100B is currently the only biomarker with moderate quality evidence to support its use.

INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED (2022)

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Review Neurosciences

Prognosis and Diagnostic Biomarkers of Mild Traumatic Brain Injury: Current Status and Future Prospects

Valeria Diaz-Pacheco et al.

Summary: Mild traumatic brain injury (mTBI) is the most common type of TBI, characterized by a lack of noticeable changes in neuroimaging studies. Accurate diagnosis of mTBI is crucial due to its potential to cause post-concussion syndrome and cognitive impairments. This review focuses on the role of biomarkers in diagnosing mTBI, including protein-based markers, genetic markers, imaging markers, neurophysiological markers, and clinical trials.

JOURNAL OF ALZHEIMERS DISEASE (2022)

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Article Clinical Neurology

Micro-RNA levels and symptom profile after mild traumatic brain injury: A longitudinal cohort study

Biswadev Mitra et al.

Summary: This study aimed to assess the discriminative ability of seven miRNAs in plasma to differentiate between patients with mild traumatic brain injury (mTBI) and healthy controls. The study found differences in miRNA levels among mTBI subjects compared to healthy controls and different miRNA levels among those who had recovered compared to those reporting symptoms. The change in profiles of miRNAs was different to symptom severity, suggesting that the two measures reflect different aspects of brain injury and recovery.

JOURNAL OF CLINICAL NEUROSCIENCE (2022)

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Review Clinical Neurology

Blood GFAP as an emerging biomarker in brain and spinal cord disorders

Ahmed Abdelhak et al.

Summary: Blood-derived biomarkers, such as glial fibrillary acidic protein (GFAP), hold promise in the diagnosis and prognosis of neurological diseases. However, there are limitations that hinder the widespread clinical use of GFAP as a biomarker.

NATURE REVIEWS NEUROLOGY (2022)

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Review Biochemistry & Molecular Biology

Aquaporin 4 in Traumatic Brain Injury: From Molecular Pathways to Therapeutic Target

Ehsan Dadgostar et al.

Summary: This review summarizes the current knowledge and evidence on the relationship between AQP4 and TBI, as well as the potential mechanisms involved.

NEUROCHEMICAL RESEARCH (2022)

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Review Behavioral Sciences

Blood-based biomarkers of inflammation in mild traumatic brain injury: A systematic review

Koen Visser et al.

Summary: This systematic review summarizes clinical studies on blood-based inflammatory markers after mild traumatic brain injury (mTBI) and identifies the value of inflammatory markers as biomarkers. The review suggests a distinct systemic inflammatory response following mTBI, quantifiable within 6 hours up to 12 months post-injury.

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS (2022)

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Review Oncology

Exosomal Proteins and Lipids as Potential Biomarkers for Lung Cancer Diagnosis, Prognosis, and Treatment

Ming-Tsung Hsu et al.

Summary: Exosomes play a crucial role in intercellular communication and can be utilized as valuable tools for the diagnosis and treatment of lung cancer. This review comprehensively analyzes the protein and lipid characteristics of lung cancer-derived exosomes and explores their molecular functions and mechanisms in physiological and pathological processes.

CANCERS (2022)

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Article Neurosciences

CNS endothelial derived extracellular vesicles are biomarkers of active disease in multiple sclerosis

Michael Mazzucco et al.

Summary: This study developed a novel method to identify central nervous system (CNS) endothelial derived extracellular vesicles (EV) in human blood samples, and found that the plasma concentration of CNS endothelial derived EV was significantly increased in patients with active multiple sclerosis (MS), suggesting that it may serve as a biomarker of blood-brain barrier permeability and active disease in MS.

FLUIDS AND BARRIERS OF THE CNS (2022)

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Article Chemistry, Medicinal

Exosomes in Parkinson: Revisiting Their Pathologic Role and Potential Applications

Yassamine Ouerdane et al.

Summary: Parkinson's disease is a progressive neurodegenerative disorder characterized by bradykinesia, rigidity, and tremor. The exact mechanism leading to this disease is still not fully understood, but recent research suggests that the deposition of alpha-synuclein protein, along with mitochondrial dysfunction and oxidative stress, contribute to the death of dopaminergic neurons. Cell-to-cell communication through exosomes (EXOs) is proposed as a key mechanism in the progression of Parkinson's disease, as these intracellular vesicles transfer toxic fibrils and damaged organelles to recipient cells. EXOs also carry biomarkers that could be used for diagnosing neurological disorders, including Parkinson's, and they show potential as therapeutic carriers for treating neurodegenerative diseases.

PHARMACEUTICALS (2022)

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Review Neurosciences

Traumatic Brain Injury and Risk of Neurodegenerative Disorder

Benjamin L. Brett et al.

Summary: This article reviews the evidence for traumatic brain injury (TBI) as a risk factor for neurodegenerative disorders, including Alzheimer's dementia and Parkinson's disease, in clinical and neuropathological studies. It also describes the dynamic interactions between acute response to injury and chronic processes that may be involved in TBI-related pathogenesis and progression of neurodegeneration.

BIOLOGICAL PSYCHIATRY (2022)

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Review Cell Biology

In Vivo Targeting of the Neurovascular Unit: Challenges and Advancements

Oandy Naranjo et al.

Summary: The blood-brain barrier is crucial for maintaining the homeostasis of the central nervous system, and its functions are carried out by the cells of the neurovascular unit, including endothelial cells, pericytes, astrocytes, microglia, basement membrane, and neurons. These cells work together to regulate neurovascular coupling, BBB integrity, and transendothelial fluid transport.

CELLULAR AND MOLECULAR NEUROBIOLOGY (2022)

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Article Cell Biology

Local regulation of extracellular vesicle traffic by the synaptic endocytic machinery

Cassandra R. Blanchette et al.

Summary: Endocytic machinery plays an unexpected role in maintaining a release-competent pool of extracellular vesicle (EV) cargoes at synapses. It regulates EV cargo levels by opposing the endosomal retromer complex and acts upstream of synaptic cargo removal by retrograde axonal transport. This discovery reveals a novel molecular mechanism that promotes cargo loading into synaptic EVs.

JOURNAL OF CELL BIOLOGY (2022)

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Review Medicine, Research & Experimental

Exosomes as bio-inspired nanocarriers for RNA delivery: preparation and applications

Ala Amiri et al.

Summary: Nanocarriers, especially exosomes, have the potential to overcome barriers in drug delivery due to their stability and inherent capability to shuttle biomolecules. However, research on exosomes as RNA delivery systems, particularly for mRNA, is limited. Therefore, it is important to investigate the application of exosomes in mRNA-based therapies.

JOURNAL OF TRANSLATIONAL MEDICINE (2022)

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Review Neurosciences

A Literature Review of Traumatic Brain Injury Biomarkers

Hazem S. Ghaith et al.

Summary: Research into TBI biomarkers has accelerated in the past decade, but there is still a need to develop novel biomarkers entirely correlating with TBI pathologies; extracellular vesicles and miRNA are considered as promising candidates to overcome the limitations of traditional blood and CSF assays.

MOLECULAR NEUROBIOLOGY (2022)

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Review Cell Biology

Noncoding RNA as Diagnostic and Prognostic Biomarkers in Cerebrovascular Disease

Ruiyuan Weng et al.

Summary: Noncoding RNAs play a crucial role in cerebrovascular diseases and have the potential to serve as new biomarkers for early detection and prognosis.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2022)

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Article Multidisciplinary Sciences

Extracellular vesicle neurofilament light is elevated within the first 12-months following traumatic brain injury in a U.S military population

Vivian A. Guedes et al.

Summary: This study investigates the levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in blood samples of patients with traumatic brain injury (TBI). The results show that NfL levels were higher in patients with more severe TBI within one year after the injury. NfL could serve as a potential diagnostic biomarker for TBI severity.

SCIENTIFIC REPORTS (2022)

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Review Geriatrics & Gerontology

Microglia and Neuroinflammation: Crucial Pathological Mechanisms in Traumatic Brain Injury-Induced Neurodegeneration

Fangjie Shao et al.

Summary: Traumatic brain injury (TBI) is a common disease in the central nervous system with high mortality and morbidity. Patients with TBI often suffer from neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. The pathological mechanisms connecting these two processes are not fully understood. Further investigation of the pathophysiological mechanisms of TBI and TBI-induced neurodegeneration is crucial for developing accurate treatment options for these notorious consequences.

FRONTIERS IN AGING NEUROSCIENCE (2022)

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Review Pharmacology & Pharmacy

Challenges in the Development of Drug Delivery Systems Based on Small Extracellular Vesicles for Therapy of Brain Diseases

Gecioni Loch-Neckel et al.

Summary: sEVs, as a drug delivery system, possess desirable features and can be used to treat neurodegeneration associated with CNS diseases.

FRONTIERS IN PHARMACOLOGY (2022)

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Review Neurosciences

A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin

Neelam Younas et al.

Summary: This article reviews the heterogeneity of neurodegenerative diseases and the role of extracellular vesicles in intercellular communication. Exosomes have the potential to be used as biomarkers for the diagnosis and treatment of these diseases, but the lack of standardized and efficient methods for their isolation and detection is a challenge.

TRANSLATIONAL NEURODEGENERATION (2022)

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Review Medicine, General & Internal

Post-Concussion Syndrome and Chronic Traumatic Encephalopathy: Narrative Review on the Neuropathology, Neuroimaging and Fluid Biomarkers

Ioannis Mavroudis et al.

Summary: Traumatic brain injury is a significant public health issue with both short-term and long-term consequences, including neurodegenerative diseases. Recent studies have shown that even mild head injuries can increase the risk of cognitive impairment and neurodegenerative diseases in later life. The development of specific and non-invasive diagnostic biomarkers for chronic traumatic encephalopathy (CTE) is crucial for preventive medicine.

DIAGNOSTICS (2022)

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Review Biology

Overview and Update on Extracellular Vesicles: Considerations on Exosomes and Their Application in Modern Medicine

Maria Antonietta Di Bella

Summary: Exosomes are a subpopulation of extracellular vesicles that play a key role in regulating various pathophysiological processes. They have potential therapeutic and diagnostic applications due to their superior biocompatibility and stability. This article provides an overview of exosome biogenesis, structural characteristics, isolation and detection methods, and discusses the obstacles in using exosomes as delivery systems. Understanding the mechanisms of cell-to-cell communication mediated by extracellular vesicles is important for both basic science and medicine. Future investigations are required before translating exosome applications to clinical settings.

BIOLOGY-BASEL (2022)

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Article Biology

Small but Mighty-Exosomes, Novel Intercellular Messengers in Neurodegeneration

Meena Kumari et al.

Summary: Exosomes are intercellular messengers that can transfer lipids, proteins, and RNA to other cells, playing a crucial role in maintaining CNS homeostasis and neurodegenerative diseases. They have the potential to be used as therapeutic agents for drug delivery to the brain, as they can cross the blood-brain barrier.

BIOLOGY-BASEL (2022)

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Article Neurosciences

Phosphorylation of Truncated Tau Promotes Abnormal Native Tau Pathology and Neurodegeneration

Longfei Li et al.

Summary: Abnormal posttranslational modifications of tau, including phosphorylation and truncation, play important roles in tau pathology and neurodegeneration. Phosphorylation of truncated tau significantly fosters endogenous tau pathology and neurodegeneration.

MOLECULAR NEUROBIOLOGY (2022)

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Article Neurosciences

Association of day-of-injury serum glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury

Jacqueline R. Kulbe et al.

Summary: This study aimed to determine whether two day-of-injury blood-based biomarkers are predictive of posttraumatic stress disorder (PTSD). The results showed that elevated day-of-injury serum GFAP levels are associated with a reduced risk of PTSD after mild TBI.

NEUROPSYCHOPHARMACOLOGY (2022)

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Review Cell Biology

Mesenchymal Stem Cell Therapy: A Potential Treatment Targeting Pathological Manifestations of Traumatic Brain Injury

Kaige Zhang et al.

Summary: Traumatic brain injury (TBI) is a significant part of acute brain injuries and a major cause of disability globally. The therapy based on mesenchymal stromal cells shows potential in treating TBI by targeting its pathological processes.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2022)

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Review Clinical Neurology

The prognostic significance of biomarkers in cerebrospinal fluid following severe traumatic brain injury: a systematic review and meta-analysis

Victor Schwartz Hvingelby et al.

Summary: This review and meta-analysis examined the relationship between cerebrospinal fluid markers and patient outcomes in severe traumatic brain injury (sTBI). The findings suggest that five biomarkers are correlated with unfavorable outcomes in sTBI patients. However, the limited number of included studies makes it difficult to draw further conclusions based on these findings.

NEUROSURGICAL REVIEW (2022)

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Article Biology

Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway

Zhen-Wen Zhang et al.

Summary: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Research suggests that exosomes derived from human umbilical cord mesenchymal stem cells (HUCMSCs) could be a promising therapeutic strategy for TBI. Experiments on rats showed that HUCMSCs-derived exosomes improved sensorimotor function and spatial learning, reduced inflammatory response, and promoted neuron regeneration in the injured cortex after TBI.

OPEN LIFE SCIENCES (2022)

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Article Rehabilitation

Blood Biomarkers in Brain Injury Medicine

William R. McBride et al.

Summary: This review explores blood-based biomarkers with potential clinical applications, particularly in the subacute to chronic phase of TBI recovery. Recent findings suggest that emerging non-proteomic biomarkers play a crucial role in accurate diagnosis and prognostic capabilities, and there is substantial overlap between TBI-related and dementia-related blood biomarkers. Blood-based biomarkers hold the most promise as non-invasive biomarkers widely available to clinicians in the field of Brain Injury Medicine.

CURRENT PHYSICAL MEDICINE AND REHABILITATION REPORTS (2022)

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Review Critical Care Medicine

Blood-Based Protein Biomarkers for the Management of Traumatic Brain Injuries in Adults Presenting to Emergency Departments with Mild Brain Injury: A Living Systematic Review and Meta-Analysis

Stefania Mondello et al.

Summary: The study found that measurement of S100B can help informed decision making in the emergency department, but there is insufficient evidence that any of the other markers is ready for clinical application. Serious problems in the design, analysis, and reporting of many of the studies were identified, as well as substantial heterogeneity and research gaps.

JOURNAL OF NEUROTRAUMA (2021)

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Article Clinical Neurology

Definition and epidemiology of mild traumatic brain injury

C. Lefevre-Dognin et al.

Summary: This article reviews the definitions and epidemiology of mild traumatic brain injury, noting the controversy surrounding the definition and the significant variation in incidence rates between countries. Mild TBI is a major public health concern with changing epidemiological patterns.

NEUROCHIRURGIE (2021)

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Article Clinical Neurology

Plasma extracellular vesicles as a source of biomarkers in traumatic brain injury

Ross C. Puffer et al.

Summary: This study isolated extracellular vesicles (EVs) from plasma of traumatic brain injury (TBI) patients and identified higher GFAP concentration and differential expression of miRNAs in EVs from patients with altered consciousness, suggesting the potential utility of EVs as a source of TBI biomarkers. Further evaluation in larger patient cohorts is recommended.

JOURNAL OF NEUROSURGERY (2021)

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Review Oncology

The role of exosomes in liquid biopsy for cancer diagnosis and prognosis prediction

Shiyu Li et al.

Summary: Exosomes, as a new type of liquid biopsy, have the potential to be diagnostic or prognostic biomarkers by delivering cargos including nucleic acids and protein, involving in tumorigenesis, tumor growth, metastasis, and drug resistance.

INTERNATIONAL JOURNAL OF CANCER (2021)

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Review Biochemistry & Molecular Biology

Exosomes in Parkinson disease

Jennifer R. Pinnell et al.

Summary: Exosomes play a potential role in the propagation of pathological alpha-synuclein in Parkinson's disease. They have the ability to transport proteins and genetic material between cells, and may serve as biomarkers and delivery vectors for therapeutics in PD.

JOURNAL OF NEUROCHEMISTRY (2021)

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Review Critical Care Medicine

Biofluid Biomarkers in Traumatic Brain Injury: A Systematic Scoping Review

Maryam Edalatfar et al.

Summary: This study conducted a systematic scoping review of evidence on biofluid-based biochemical markers of traumatic brain injuries (TBI), extracting 540 biomarkers from 1036 studies across 19 distinct categories. Cytokines, coagulation tests, and nerve tissue proteins were the most commonly investigated biomarker categories, with cortisol being the most frequently measured biomarker across blood, cerebrospinal fluid, urine, and saliva. The studies primarily focused on adult populations with severe and blunt injuries.

NEUROCRITICAL CARE (2021)

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Review Engineering, Biomedical

Extracellular vesicles: A bright star of nanomedicine

Peipei Wu et al.

Summary: Extracellular vesicles play a crucial role in disease treatment and diagnosis, with engineered design enhancing their therapeutic capability and diagnostic imaging potential.

BIOMATERIALS (2021)

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Article Clinical Neurology

Neurofilament light predicts neurological outcome after subarachnoid haemorrhage

Patrick Garland et al.

Summary: NF-L is a strong predictive marker for SAH clinical outcome, independent of WFNS score, and is a promising surrogate end point in clinical trials.

BRAIN (2021)

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Article Biochemistry & Molecular Biology

Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury

Shalini Das Gupta et al.

Summary: The study identified plasma miR-9-3p and miR-136-3p as promising biomarker candidates for mTBI, showing potential for distinguishing mTBI patients with high sensitivity and specificity. Further validation in a larger patient population is needed to confirm their diagnostic utility.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Biochemistry & Molecular Biology

Protective Effects of Aquaporin-4 Deficiency on Longer-term Neurological Outcomes in a Mouse Model

Xiaosong Liu et al.

Summary: The study demonstrates that AQP4 deficiency can alleviate brain edema and neurological deficits in TBI patients, improve cognitive outcomes, and enhance longer-term neurological results.

NEUROCHEMICAL RESEARCH (2021)

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Article Multidisciplinary Sciences

Extracellular vesicle concentrations of glial fibrillary acidic protein and neurofilament light measured 1 year after traumatic brain injury

Spencer Flynn et al.

Summary: The study found that blood-derived EV concentrations of GFAP and NfL are higher in TBI patients compared to controls even 1 year after injury, and are related to injury severity and poor recovery outcomes, suggesting that TBIs alter the activity of these biomarkers, likely contributing to individual variability in recovery.

SCIENTIFIC REPORTS (2021)

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Article Medicine, General & Internal

Study protocol for investigating the performance of an automated blood test measuring GFAP and UCH-L1 in a prospective observational cohort of patients with mild traumatic brain injury: European BRAINI study

Marion Richard et al.

Summary: This study evaluates the diagnostic accuracy of an automated assay for measuring serum GFAP and UCH-L1 concentrations in discriminating between patients with positive and negative brain CT scan findings. The results will help predict patients' neurological status and quality of life.

BMJ OPEN (2021)

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Review Cell Biology

The exosome journey: from biogenesis to uptake and intracellular signalling

Sonam Gurung et al.

Summary: Exosomes have vast potential in clinical applications, and understanding their biology is crucial. The processes of exosome biogenesis, transport, and uptake involve numerous influencing factors.

CELL COMMUNICATION AND SIGNALING (2021)

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Article Pharmacology & Pharmacy

Extracellular Vesicle Proteins and MicroRNAs Are Linked to Chronic Post-Traumatic Stress Disorder Symptoms in Service Members and Veterans With Mild Traumatic Brain Injury

Vivian A. Guedes et al.

Summary: The study found that levels of neurofilament light chain (NfL) were associated with the severity of PTSD symptoms in participants with remote mTBI, and specific miRNAs were also linked to the severity of PTSD symptoms. This suggests possible signaling pathways linked to the development of persistent PTSD symptoms after TBI.

FRONTIERS IN PHARMACOLOGY (2021)

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Review Cell Biology

Exosomes in Ageing and Motor Neurone Disease: Biogenesis, Uptake Mechanisms, Modifications in Disease and Uses in the Development of Biomarkers and Therapeutics

Ekene Anakor et al.

Summary: Intercellular communication between neurons and their surrounding cells occurs through secretion of soluble molecules or release of vesicles like exosomes, which play a role in maintaining brain homeostasis. Exosomes are suspected to spread toxic proteins in neurodegenerative conditions associated with aging. This review focuses on the role of exosomes in aging and specifically in ALS, highlighting their potential use as biomarkers and therapeutics for the disease.

CELLS (2021)

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Review Cell Biology

A brief history of nearly EV-erything - The rise and rise of extracellular vesicles

Yvonne Couch et al.

Summary: Extracellular vesicles (EVs) are small cargo-bearing vesicles released by cells into the extracellular space, serving as a complex cell-to-cell communication mechanism that transfers functional cargo and influences biological processes, with deregulation in disease. The field of EVs has grown exponentially over the past two decades with an organized community, but still faces key challenges.

JOURNAL OF EXTRACELLULAR VESICLES (2021)

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Article Critical Care Medicine

MiR-17-92 Cluster-Enriched Exosomes Derived from Human Bone Marrow Mesenchymal Stromal Cells Improve Tissue and Functional Recovery in Rats after Traumatic Brain Injury

Yanlu Zhang et al.

Summary: Exosomes enriched with miR-17-92 cluster have a significantly better effect on improving functional recovery after TBI compared with Exo-empty, likely by reducing neuroinflammation and enhancing endogenous angiogenesis and neurogenesis. Engineering specific miRNA in exosomes may provide a novel therapeutic strategy for management of unilateral moderate cortical contusion TBI.

JOURNAL OF NEUROTRAUMA (2021)

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Article Pharmacology & Pharmacy

Ginsenoside Rg1 ameliorates blood-brain barrier disruption and traumatic brain injury via attenuating macrophages derived exosomes miR-21 release

Kefeng Zhai et al.

Summary: During traumatic brain injury, increased expression of circulatory miR-21 can serve as a diagnostic feature. Low levels of exosome-miR-21 in the brain can improve neuroinflammation and BBB permeability, and Rg1 can protect BBB integrity by inhibiting the release of Exos-miR-21.

ACTA PHARMACEUTICA SINICA B (2021)

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Review Cell Biology

Exosomes: Innocent Bystanders or Critical Culprits in Neurodegenerative Diseases

Margarida Beatriz et al.

Summary: Extracellular vesicles (EVs) are nano-sized particles released by cells that facilitate intercellular communication by transferring biological material. Recent studies suggest that exosomes, a type of EV, play a crucial role in the spread of neurodegenerative diseases by carrying genetic material and proteins. This review focuses on the role of exosomes in central nervous system homeostasis, their potential contribution to neurodegenerative diseases, the use of exosome cargo as disease biomarkers, and the benefits of circulating CNS-derived exosomes in plasma.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Biochemistry & Molecular Biology

Biomarkers for neurodegenerative diseases

Oskar Hansson

Summary: Biomarkers for neurodegenerative diseases play a crucial role in improving diagnostic workup and therapy monitoring, with emerging blood-based markers and discussions on their implementation in clinical practice and trials.

NATURE MEDICINE (2021)

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Article Neurosciences

Several miRNAs derived from serum extracellular vesicles are potential biomarkers for early diagnosis and progression of Parkinson's disease

Shulei He et al.

Summary: This study identified 6 serum EV-derived miRNAs that may serve as potential biomarkers for PD progression and early diagnosis in populations, demonstrating their potential clinical utility.

TRANSLATIONAL NEURODEGENERATION (2021)

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Article Geriatrics & Gerontology

Proteomic Profiling of Extracellular Vesicles Separated from Plasma of Former National Football League Players at Risk for Chronic Traumatic Encephalopathy

Satoshi Muraoka et al.

Summary: The study examined the protein profiles of EVs separated from the plasma of former NFL players at risk for CTE, identifying a potential combination of COL6A3, RELN, and COL6A1 as diagnostic biomarkers for CTE. Machine learning analysis showed a high accuracy of 85% in distinguishing former NFL players from controls. This data provides valuable insights into CTE diagnosis and potential biomarkers.

AGING AND DISEASE (2021)

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Review Biochemistry & Molecular Biology

Extracellular Vesicles in neural cell interaction and CNS homeostasis

Andrea Schnatz et al.

Summary: Extracellular vesicles (EVs) play a crucial role in CNS homeostasis by serving as versatile messengers in intercellular communication. They are involved in various physiological processes such as clearance of cellular components, mediation of trophic support, promotion of axonal maintenance, and modulation of neuroinflammation. Novel transgenic models and imaging technologies provide deeper insights into the functions and mechanisms of EVs in the nervous system.

FASEB BIOADVANCES (2021)

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Review Biochemistry & Molecular Biology

The role of extracellular vesicles in the physiological and pathological regulation of the blood-brain barrier

Sara Busatto et al.

Summary: Extracellular vesicles are biological nanoparticles secreted by cells that can transport bioactive substances, serving as both a potential source of diagnostic biomarkers and a promising class of nanovehicles for drug delivery. They play a crucial role in maintaining the blood-brain barrier under normal physiological and pathological conditions.

FASEB BIOADVANCES (2021)

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Review Biochemistry & Molecular Biology

Regulation of exosome production and cargo sorting

Hong Wei et al.

Summary: Cellular communication through the exchange of biological information, mainly in the form of proteins and RNAs, is mediated by extracellular vesicles like exosomes. Understanding the molecular mechanisms of exosome secretion and cargo sorting is crucial for shedding light on their physiological and pathological functions, as well as for exploring potential therapeutic opportunities in clinical applications.

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2021)

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Article Neurosciences

Neuroinflammation and blood-brain barrier disruption following traumatic brain injury: Pathophysiology and potential therapeutic targets

Suraj Sulhan et al.

JOURNAL OF NEUROSCIENCE RESEARCH (2020)

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Article Clinical Neurology

Elevated Tau in Military Personnel Relates to Chronic Symptoms Following Traumatic Brain Injury

Cassandra L. Pattinson et al.

JOURNAL OF HEAD TRAUMA REHABILITATION (2020)

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Article Critical Care Medicine

Multi-Dimensional Mapping of Brain-Derived Extracellular Vesicle MicroRNA Biomarker for Traumatic Brain Injury Diagnostics

Matthew Hemphill et al.

JOURNAL OF NEUROTRAUMA (2020)

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Article Critical Care Medicine

Neuron-Derived Plasma Exosome Proteins after Remote Traumatic Brain Injury

Edward J. Goetzl et al.

JOURNAL OF NEUROTRAUMA (2020)

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Article Rehabilitation

Management of Concussion and Mild Traumatic Brain Injury: A Synthesis of Practice Guidelines

Noah D. Silverberg et al.

ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2020)

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Article Biotechnology & Applied Microbiology

Increased Microglial Exosomal miR-124-3p Alleviates Neurodegeneration and Improves Cognitive Outcome after rmTBI

Xintong Ge et al.

MOLECULAR THERAPY (2020)

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Article Biochemistry & Molecular Biology

Can Mesenchymal Stem Cells Act Multipotential in Traumatic Brain Injury?

Fatemeh Dehghanian et al.

JOURNAL OF MOLECULAR NEUROSCIENCE (2020)

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Article Critical Care Medicine

Alterations in Plasma microRNA and Protein Levels in War Veterans with Chronic Mild Traumatic Brain Injury

Vikas Ghai et al.

JOURNAL OF NEUROTRAUMA (2020)

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Review Medicine, General & Internal

The Role of Blood Biomarkers for Magnetic Resonance Imaging Diagnosis of Traumatic Brain Injury

John K. Yue et al.

MEDICINA-LITHUANIA (2020)

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Article Cell Biology

Inside(sight) of tiny communicator: exosome biogenesis, secretion, and uptake

Anshul S. Jadli et al.

MOLECULAR AND CELLULAR BIOCHEMISTRY (2020)

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Review Multidisciplinary Sciences

The biology, function, and biomedical applications of exosomes

Raghu Kalluri et al.

SCIENCE (2020)

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Article Clinical Neurology

A Prospective Study of Acute Blood-Based Biomarkers for Sport-Related Concussion

Timothy B. Meier et al.

ANNALS OF NEUROLOGY (2020)

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Article Clinical Neurology

A longitudinal study on α-synuclein in plasma neuronal exosomes as a biomarker for Parkinson's disease development and progression

M. Niu et al.

EUROPEAN JOURNAL OF NEUROLOGY (2020)

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Article Immunology

Astrocyte-derived exosomes enriched with miR-873a-5p inhibit neuroinflammation via microglia phenotype modulation after traumatic brain injury

Xiaobing Long et al.

JOURNAL OF NEUROINFLAMMATION (2020)

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Review Critical Care Medicine

Clinical Applications of Extracellular Vesicles in the Diagnosis and Treatment of Traumatic Brain Injury

Kryshawna Beard et al.

JOURNAL OF NEUROTRAUMA (2020)

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Review Cell Biology

Targeting and Crossing the Blood-Brain Barrier with Extracellular Vesicles

Julien Saint-Pol et al.

CELLS (2020)

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Article Cell Biology

Circulating Brain Injury Exosomal Proteins following Moderate-to-Severe Traumatic Brain Injury: Temporal Profile, Outcome Prediction and Therapy Implications

Stefania Mondello et al.

CELLS (2020)

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Article Clinical Neurology

Exosomal neurofilament light: A prognostic biomarker for remote symptoms after mild traumatic brain injury?

Vivian A. Guedes et al.

NEUROLOGY (2020)

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Article Neurosciences

Persistence of post-concussion symptoms in patients with mild traumatic brain injury and no psychiatric history in the emergency department

Narges Mehrolhassani et al.

BRAIN INJURY (2020)

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Article Medicine, General & Internal

Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study

Endre Czeiter et al.

EBIOMEDICINE (2020)

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Review Cell Biology

Exosome Circuitry During (De)(Re)Myelination of the Central Nervous System

Helena S. Domingues et al.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2020)

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Review Biochemistry & Molecular Biology

Extracellular Vesicles in Acute Stroke Diagnostics

Katrine Tang Stenz et al.

BIOMEDICINES (2020)

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Review Cell Biology

T regulatory cells-derived extracellular vesicles and their contribution to the generation of immune tolerance

Carolina Rojas et al.

JOURNAL OF LEUKOCYTE BIOLOGY (2020)

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Article Cell Biology

MSC-derived exosomes promote recovery from traumatic brain injury via microglia/macrophages in rat

Yunfei Chen et al.

Aging-US (2020)

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Article

Apoptosis (programmed cell death) and its signals - A review

E. Obeng

BRAZILIAN JOURNAL OF BIOLOGY (2020)

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Article Clinical Neurology

Blood biomarkers of traumatic brain injury and cognitive impairment in older veterans

Carrie B. Peltz et al.

NEUROLOGY (2020)

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NEUROLOGY (2020)

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Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage

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Biomarker potential of brain-secreted extracellular vesicles in blood in Alzheimer's disease

AmanPreet Badhwar et al.

ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING (2020)

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Exosomes as mediators of neuron-glia communication in neuroinflammation

Maria Pascual et al.

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Alisa A. Shaimardanova et al.

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Mesenchymal Stem Cell-Derived Exosomes Improve Functional Recovery in Rats After Traumatic Brain Injury: A Dose-Response and Therapeutic Window Study

Yanlu Zhang et al.

NEUROREHABILITATION AND NEURAL REPAIR (2020)

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Plasma glial fibrillary acidic protein and neurofilament light chain, but not tau, are biomarkers of sports-related mild traumatic brain injury

Etienne Laverse et al.

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Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Evaluation and Treatment of Patients with Thoracolumbar Spine Trauma: Surgical Approaches

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Neuroprotective Strategies for Neurological Disorders by Natural Products: An update

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SNAP-25 in Serum Is Carried by Exosomes of Neuronal Origin and Is a Potential Biomarker of Alzheimer's Disease

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α-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson's disease

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Neuroimmune Crosstalk through Extracellular Vesicles in Health and Disease

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TRENDS IN NEUROSCIENCES (2019)

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Risk of Posttraumatic Stress Disorder and Major Depression in Civilian Patients After Mild Traumatic Brain Injury A TRACK-TBI Study

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JAMA PSYCHIATRY (2019)

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Loss of consciousness and altered mental state predicting depressive and post-concussive symptoms after mild traumatic brain injury

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Reassessment of Exosome Composition

Dennis K. Jeppesen et al.

CELL (2019)

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Exosome-Mediated Metastasis: Communication from a Distance

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ANNUAL REVIEW OF BIOCHEMISTRY, VOL 88 (2019)

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Andrew F. Hill

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Michael L. Levy et al.

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Assessing Neuronal and Astrocyte Derived Exosomes From Individuals With Mild Traumatic Brain Injury for Markers of Neurodegeneration and Cytotoxic Activity

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Proteomic Profiling of Extracellular Vesicles Isolated From Cerebrospinal Fluid of Former National Football League Players at Risk for Chronic Traumatic Encephalopathy

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Altered levels of plasma neuron-derived exosomes and their cargo proteins characterize acute and chronic mild traumatic brain injury

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MiR-124 Enriched Exosomes Promoted the M2 Polarization of Microglia and Enhanced Hippocampus Neurogenesis After Traumatic Brain Injury by Inhibiting TLR4 Pathway

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Concurrent Mild Traumatic Brain Injury and Posttraumatic Stress Disorder Is Associated With Elevated Tau Concentrations in Peripheral Blood Plasma

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Extracellular Vesicle Biology in Alzheimer's Disease and Related Tauopathy

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Higher exosomal phosphorylated tau and total tau among veterans with combat-related repetitive chronic mild traumatic brain injury

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Kevin K. Wang et al.

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Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons

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Glial fibrillary acidic protein elevations relate to neuroimaging abnormalities after mild TBI

Jessica Gill et al.

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Schwann cell-like differentiated adipose stem cells promote neurite outgrowth via secreted exosomes and RNA transfer

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Clinical research using extracellular vesicles: insights from the International Society for Extracellular Vesicles 2018 Annual Meeting

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Blood-Brain Barrier Dysfunction and the Pathogenesis of Alzheimer's Disease

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Bridget Martinez et al.

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Clinical validity of cerebrospinal fluid Aβ42, tau, and phospho-tau as biomarkers for Alzheimer's disease in the context of a structured 5-phase development framework

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Exosomes maintain cellular homeostasis by excreting harmful DNA from cells

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JAMA NEUROLOGY (2017)

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Potential Roles of Exosomal MicroRNAs as Diagnostic Biomarkers and Therapeutic Application in Alzheimer's Disease

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Exosomes and Homeostatic Synaptic Plasticity Are Linked to Each other and to Huntington's, Parkinson's, and Other Neurodegenerative Diseases by Database-Enabled Analyses of Comprehensively Curated Datasets

James K. T. Wang et al.

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ATP Modifies the Proteome of Extracellular Vesicles Released by Microglia and Influences Their Action on Astrocytes

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Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain injury Dynamics: A Systematic Review

Eric Peter Thelin et al.

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Tingting Xiao et al.

TRANSLATIONAL NEURODEGENERATION (2017)

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Brain-Derived Microparticles in Patients with Severe Isolated TBI

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BRAIN INJURY (2017)

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Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity

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Exosomes purified from a single cell type have diverse morphology

Davide Zabeo et al.

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Geoff Manley et al.

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Structural imaging of mild traumatic brain injury may not be enough: overview of functional and metabolic imaging of mild traumatic brain injury

Samuel S. Shin et al.

BRAIN IMAGING AND BEHAVIOR (2017)

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Amyloid-beta and tau pathology following repetitive mild traumatic brain injury

George Edwards et al.

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Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies

Anne Stuendl et al.

BRAIN (2016)

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Exosome-mediated inflammasome signaling after central nervous system injury

Juan Pablo de Rivero Vaccari et al.

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Chromatographically isolated CD63+ CD81+ extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI

Dong-ki Kim et al.

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Exosomes and other extracellular vesicles in neural cells and neurodegenerative diseases

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Schwann Cell Exosomes Mediate Neuron-Glia Communication and Enhance Axonal Regeneration

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Medicinal Chemistry Focusing on Aggregation of Amyloid-β

Youhei Sohma

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The role of vascular endothelial growth factor and vascular endothelial growth inhibitor in clinical outcome of traumatic brain injury

Min Li et al.

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Extracellular vesicles: interneural shuttles of complex messages

Eva-Maria Kraemer-Albers et al.

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Preliminary Study of Plasma Exosomal Tau as a Potential Biomarker for Chronic Traumatic Encephalopathy

Robert A. Stern et al.

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Rong Xu et al.

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Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease

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Fluid biomarkers for mild traumatic brain injury and related conditions

Henrik Zetterberg et al.

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Extracellular vesicles in neurodegenerative disease - pathogenesis to biomarkers

Alexander G. Thompson et al.

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Extracellular vesicles round off communication in the nervous system

Vivian Budnik et al.

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Cerebral amyloid-β accumulation and deposition following traumatic brain injury-A narrative review and meta-analysis of animal studies

Sabine M. Bird et al.

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Exosomes as a potential novel therapeutic tools against neurodegenerative diseases

Akvile Jarmalaviciute et al.

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Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes

Joanna Kowal et al.

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Mechanical Injury Induces Brain Endothelial-Derived Microvesicle Release: Implications for Cerebral Vascular Injury during Traumatic Brain Injury

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Potential Therapies by Stem Cell-Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche

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Traumatic brain injury increases levels of miR-21 in extracellular vesicles: implications for neuroinflammation

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Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges

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Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke

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Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients

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Cells release subpopulations of exosomes with distinct molecular and biological properties

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A Panel of Serum MiRNA Biomarkers for the Diagnosis of Severe to Mild Traumatic Brain Injury in Humans

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MiRNAs in Astrocyte-Derived Exosomes as Possible Mediators of Neuronal Plasticity

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Fluid Biomarkers of Traumatic Brain Injury and Intended Context of Use

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Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study

Massimo S. Fiandaca et al.

ALZHEIMERS & DEMENTIA (2015)

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Mechanisms of regulation of mature miRNAs

Benjamin P. Towler et al.

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Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer's disease

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Microvesicles in the brain: Biomarker, messenger or mediator?

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Effect of exosomes derived from multipluripotent mesenchyrnal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury

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Raquel C. Gardner et al.

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Brain and other nervous system disorders across the lifespan - global challenges and opportunitiesINTRODUCTION

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Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease

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Exosomes in bodily fluids are a highly stable resource of disease biomarkers

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Extracellular vesicles - Their role in the packaging and spread of misfolded proteins associated with neurodegenerative diseases

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Priming the Inflammatory Puma of the CNS ater Traumatic Brain Injury

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Extracellular Vesicles Improve Post-Stroke Neuroregeneration and Prevent Postischemic Immunosuppression

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MOLECULAR PSYCHIATRY (2015)

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PLOS ONE (2015)

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Low neural exosomal levels of cellular survival factors in Alzheimer's disease

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NUCLEIC ACIDS RESEARCH (2014)

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

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