Extracellular vesicles as biomarkers for traumatic brain injury using a 3D in vitro human brain tissue model

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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.
Funding Information
  • National Institutes of Health (P41EB027062, P41EB027062)

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