Extracellular vesicle-associated cytokines in sport-related concussion

Meier, Timothy B.; Guedes, Vivian A.; Smith, Ethan G.; Sass, Dilorom; Mithani, Sara; Vorn, Rany; Savitz, Jonathan; Teague, T. Kent; McCrea, Michael; Gill, Jessica

doi:10.1016/j.bbi.2021.11.015

Cited by 10 publications

(20 citation statements)

References 25 publications

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“…Thirty-one papers found changes in blood biomarkers that significantly discriminated between SRC and controls (and/or preinjury baseline levels) 18–48. Similar alterations were found in saliva,49 50 urine,51 52 and CSF53 54 studies.…”

Section: Resultsmentioning

confidence: 70%

Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review

et al. 2023

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ObjectiveDetermine the role of fluid-based biomarkers, advanced neuroimaging, genetic testing and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion (SRC).DesignSystematic review.Data sourcesSearches of seven databases from 1 January 2001 through 24 March 2022 using keywords and index terms relevant to concussion, sports and neurobiological recovery. Separate reviews were conducted for studies involving neuroimaging, fluid biomarkers, genetic testing and emerging technologies. A standardised method and data extraction tool was used to document the study design, population, methodology and results. Reviewers also rated the risk of bias and quality of each study.Eligibility criteria for selecting studiesStudies were included if they: (1) were published in English; (2) represented original research; (3) involved human research; (4) pertained only to SRC; (5) included data involving neuroimaging (including electrophysiological testing), fluid biomarkers or genetic testing or other advanced technologies used to assess neurobiological recovery after SRC; (6) had a minimum of one data collection point within 6 months post-SRC; and (7) contained a minimum sample size of 10 participants.ResultsA total of 205 studies met inclusion criteria, including 81 neuroimaging, 50 fluid biomarkers, 5 genetic testing, 73 advanced technologies studies (4 studies overlapped two separate domains). Numerous studies have demonstrated the ability of neuroimaging and fluid-based biomarkers to detect the acute effects of concussion and to track neurobiological recovery after injury. Recent studies have also reported on the diagnostic and prognostic performance of emerging technologies in the assessment of SRC. In sum, the available evidence reinforces the theory that physiological recovery may persist beyond clinical recovery after SRC. The potential role of genetic testing remains unclear based on limited research.ConclusionsAdvanced neuroimaging, fluid-based biomarkers, genetic testing and emerging technologies are valuable research tools for the study of SRC, but there is not sufficient evidence to recommend their use in clinical practice.PROSPERO registration numberCRD42020164558.

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Section: Resultsmentioning

confidence: 70%

Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review

et al. 2023

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“…In addition to CI, several studies have also identified EVs cargo links with neuropsychiatric symptoms (Gill et al, 2018b). It has been reported that NDE tau and NFL markers are also associated with PCS symptoms and PTSD (Kenney et al, 2018;Pattinson et al, 2019;Guedes et al, 2020bGuedes et al, , 2021Guedes et al, , 2022. Some studies have also reported an increased NDE, and total exosomal levels of p-tau and total tau in patients with mild TBIs are associated with increased PTSD symptoms (Kenney et al, 2018;Gill et al, 2018b).…”

Section: Evs As Potential Predictors Of Functional Outcomes In Tbimentioning

confidence: 99%

“…Neurofilament light chain (NFL), a structural scaffolding protein abundantly expressed in long myelinated axons, is one of the most studied biomarkers due to axonal injury caused by trauma (Lee et al, 2020). NFL levels in plasma-derived exosomes have been shown to be higher in mild, moderate, and severe TBI patients at different time points following damage compared to controls (Mondello et al, 2020;Peltz et al, 2020;Guedes et al, 2020bGuedes et al, , 2021Guedes et al, , 2022 indicating exosomal NFL measurements are detectable in TBI's acute and chronic course.…”

Section: Blood-based Evs As Biomarker Reservoirs For DI Erent Severit...mentioning

confidence: 99%

“…Several studies have sought to find biomarkers to guide treatments and identify people at the highest risk of poor recovery and persistent sequelae (Gill et al, 2018a ; Nitta et al, 2019 ; Czeiter et al, 2020 ; Shahim et al, 2020 ). Several research groups have investigated candidate biomarkers detected in serum, plasma, and other body fluids (Sharma et al, 2017 ; Wang K. K. et al, 2018 ; McBride et al, 2022 ; Meier et al, 2022 ; Visser et al, 2022 ). The majority of investigations have concentrated on neuronal and astrocyte-derived proteins (Laverse et al, 2020 ; Meier et al, 2020 ; Mondello et al, 2020 ; Flynn et al, 2021 ; Garland et al, 2021 ; Richard et al, 2021 ).…”

Section: Extracellular Vesicles and Tbimentioning

confidence: 99%

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

Khan

Asim²,

El‐Menyar³

et al. 2022

Front. Aging Neurosci.

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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.

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“…Manganese activates microglia, which propagate ASC and IL-1β by releasing EVs ( 137 ). Additionally, hydrostatic pressure increases the concentration of pro-inflammatory mediators in microglia-derived EVs ( 138 ), and circulating EVs in players with sport-related concussion express high levels of IL-6 compared with uninjured players ( 139 ). Taken together, EVs are involved in immune cell activation and inflammatory dissemination via bioactive compounds such as miRNAs and cytokines.…”

Section: Extracellular Vesicles and Immune Cell Activation In Traumat...mentioning

confidence: 99%

Neuroinflammation of traumatic brain injury: Roles of extracellular vesicles

Liu

Zhang²,

Cao³

et al. 2023

Front. Immunol.

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Traumatic brain injury (TBI) is a major cause of neurological disorder or death, with a heavy burden on individuals and families. While sustained primary insult leads to damage, subsequent secondary events are considered key pathophysiological characteristics post-TBI, and the inflammatory response is a prominent contributor to the secondary cascade. Neuroinflammation is a multifaceted physiological response and exerts both positive and negative effects on TBI. Extracellular vesicles (EVs), as messengers for intercellular communication, are involved in biological and pathological processes in central nervous system (CNS) diseases and injuries. The number and characteristics of EVs and their cargo in the CNS and peripheral circulation undergo tremendous changes in response to TBI, and these EVs regulate neuroinflammatory reactions by activating prominent receptors on receptor cells or delivering pro- or anti-inflammatory cargo to receptor cells. The purpose of this review is to discuss the possible neuroinflammatory mechanisms of EVs and loading in the context of TBI. Furthermore, we summarize the potential role of diverse types of cell-derived EVs in inflammation following TBI.

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Extracellular vesicle-associated cytokines in sport-related concussion

Cited by 10 publications

References 25 publications

Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review

Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review

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

Neuroinflammation of traumatic brain injury: Roles of extracellular vesicles

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