Quercetin Protects Blood–Brain Barrier Integrity and Maintains Microvascular Permeability Following Traumatic Brain Injury

作者：Bobby Darnell Robinson, Antonia Yeager, Angela Lomas, Gabriela Seplovich, Chinchusha Anasooya Shaji, Katie Wiggins‐Dohlvik, Jason H. Huang, Claire L. Isbell, Binu Tharakan · 发表于：Neurocritical Care · 年份：2025 · DOI：10.1007/s12028-025-02315-z · 被引用次数：6 · 研究领域：Barrier Structure and Function Studies、Traumatic Brain Injury and Neurovascular Disturbances、Neuroinflammation and Neurodegeneration Mechanisms

Abstract Background Cerebral edema is a consequential outcome of traumatic brain injury (TBI) and may lead to intracranial hypertension, necessitating urgent medical attention. One of the primary causes of cerebral edema is microvascular hyperpermeability, characterized by excessive leakage of intravascular fluid and proteins via blood–brain barrier (BBB) dysregulation. Prolonged activation of reactive oxygen species (ROS) formation and inflammatory pathways due to BBB hyperpermeability results in poor patient outcomes. The primary goal of this study was to ascertain if quercetin, a bioflavonoid plant pigment, would protect against BBB breakdown and hyperpermeability in the acute context following TBI. Methods We used a mixed in vitro and in vivo model to test the effects of quercetin pretreatment on endothelial cell tight junctions in murine models of TBI and stress-induced hyperpermeability. Hydrogen peroxide (H 2 O 2 ), a key contributor of secondary injuries following TBI, was used as an inducer of oxidative stress in cerebral endothelial cells in vitro. BBB tight junction/cytoskeletal integrity was assessed using immunofluorescence of junctional proteins zonula occludens-1, β-catenin, and vascular endothelial–cadherin, alongside filamentous actin labeling and a monolayer permeability assay. Intracellular ROS and H 2 O 2 levels were determined using fluorescent probes. In vivo experiments consisted of intravital microscopy of brain pial vasculature in a mouse model of TBI...