Contribution of brain pericytes to neuroinflammation following repetitive head trauma

作者：Arianna Cembran, Maxwell Eisenbaum, Daniel Paris, Michael Mullan, Fiona Crawford, Scott Ferguson, Corbin Bachmeier · 发表于：Journal of Inflammation · 年份：2025 · DOI：10.1186/s12950-025-00439-9 · 被引用次数：12 · 研究领域：Barrier Structure and Function Studies、Neuroinflammation and Neurodegeneration Mechanisms、Traumatic Brain Injury and Neurovascular Disturbances

BACKGROUND: Neuroinflammation is a prominent pathological hallmark of traumatic brain injury (TBI) and glia cells have been widely characterized in the onset or progression of brain inflammation. While an effect of inflammation on cerebrovascular breakdown has been observed, little is known about the specific contribution of brain pericytes to the inflammatory response in TBI. Here, we focused on studying the pericyte response to inflammatory stimuli commonly found in the brain following TBI. METHODS: Mouse brain vascular pericytes were exposed to IL-1β, TNF-α and IFN-γ for 2 h and 24 h and probed for markers of pericyte health and a panel of inflammatory mediators. As the platelet-derived growth factor (PDGF) pathway is critical to pericyte function, we also assessed the effect of PDGF-BB stimulation on the inflammatory response in pericytes. Cultured pericytes were treated with PDGF-BB (10 ng/mL) prior to, simultaneously, and following inflammatory insult. To further investigate their role in brain immunosurveillance, we analyzed the cytokine secretome in mouse pericyte cultures treated with PDGF-BB, as well as in brain vascular pericytes isolated from repetitive mild TBI (r-mTBI) mice that were fed phenytoin-enriched chow, an inducer of PDGF-BB secretion. RESULTS: Cytokine stimulation with TNF-α, IL-1β, and IFN-γ for 2 and 24 h led to significant upregulation of PDGFRβ in cultured pericytes, with an 8-fold increase after 24 h. MTT assays showed no significant change in cel...