{"title":"Extracellular vesicles as biomarkers for traumatic brain injury using a 3D in vitro human brain tissue model.","authors":"Peter Hsi, Vishal Tandon, David L Kaplan","doi":"10.1038/s41598-025-04835-2","DOIUrl":null,"url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a significant health challenge worldwide, with current diagnostics and treatment falling short due to the complex pathophysiology involved. Extracellular vesicles (EVs) play a crucial role in brain injury response and are promising biomarkers for understanding the progression of TBI. A 3D in vitro human brain tissue model, comprising neurons, astrocytes, and microglia was utilized to simulate TBI and investigate EV responses. EVs were isolated at multiple acute timepoints post-injury and microRNA (miRNA) profiling revealed transient dysregulation of several miRNAs that aligned with clinical and in vivo studies. Pathway analysis revealed that these miRNAs are associated with the phosphoinositide 3-kinase / protein kinase B (PI3K / AKT) cell signaling pathway, a key regulator of neuroprotection, cell survival and injury response in TBI. The data suggest that temporal dysregulation of miRNAs plays a critical role in driving cellular responses following tissue injury and may serve as an initial snapshot of signaling following TBI, informing future investigations into long-term injury progression. Additionally, these findings demonstrate the utility of using an in vitro brain tissue model to study EVs in TBI to help identify potential biomarkers for clinical utility.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"26940"},"PeriodicalIF":3.9000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289892/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scientific Reports","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41598-025-04835-2","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
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Abstract
Traumatic brain injury (TBI) is a significant health challenge worldwide, with current diagnostics and treatment falling short due to the complex pathophysiology involved. Extracellular vesicles (EVs) play a crucial role in brain injury response and are promising biomarkers for understanding the progression of TBI. A 3D in vitro human brain tissue model, comprising neurons, astrocytes, and microglia was utilized to simulate TBI and investigate EV responses. EVs were isolated at multiple acute timepoints post-injury and microRNA (miRNA) profiling revealed transient dysregulation of several miRNAs that aligned with clinical and in vivo studies. Pathway analysis revealed that these miRNAs are associated with the phosphoinositide 3-kinase / protein kinase B (PI3K / AKT) cell signaling pathway, a key regulator of neuroprotection, cell survival and injury response in TBI. The data suggest that temporal dysregulation of miRNAs plays a critical role in driving cellular responses following tissue injury and may serve as an initial snapshot of signaling following TBI, informing future investigations into long-term injury progression. Additionally, these findings demonstrate the utility of using an in vitro brain tissue model to study EVs in TBI to help identify potential biomarkers for clinical utility.
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