Contribution of brain pericytes to neuroinflammation following repetitive head trauma
Abstract 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...
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BMC
2025-03-01
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| Series: | Journal of Inflammation |
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| Online Access: | https://doi.org/10.1186/s12950-025-00439-9 |
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| author | Arianna Cembran Maxwell Eisenbaum Daniel Paris Michael Mullan Fiona Crawford Scott Ferguson Corbin Bachmeier |
| author_facet | Arianna Cembran Maxwell Eisenbaum Daniel Paris Michael Mullan Fiona Crawford Scott Ferguson Corbin Bachmeier |
| author_sort | Arianna Cembran |
| collection | DOAJ |
| description | Abstract 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 cell viability, indicating that cytokine treatment did not induce cytotoxicity. Further, elevated levels of pro-inflammatory markers STAT1 and p-NFkB were observed in response to cytokine exposure, with a concurrent increase in VCAM1 and MMP9 expression. PDGF-BB treatment significantly attenuated the inflammatory response in pericytes, reducing PDGFRβ levels and the activation of inflammatory pathways, including STAT1 and NFkB. Cytokine secretion profiles also revealed that PDGF-BB, when administered post-inflammatory insult, selectively reduced pro-inflammatory cytokines such as IL-1β and IFN-γ. Additionally, phenytoin treatment in r-mTBI mice decreased IL-1β, TNF-α, IL-5, and KC/GRO levels in isolated brain pericytes, while IL-2, IL-4, and IL-6 levels were unchanged compared to untreated r-mTBI animals. Conclusions Our results indicate an immunoreactive role for brain pericytes in the propagation of neuroinflammation. Moreover, following brain insults, we found PDGF-BB stimulation can normalize pericyte function and reduce cerebrovascular inflammation, a key factor in secondary brain injury. Targeting brain pericytes may provide novel therapeutic opportunities to improve cerebrovascular health and reduce brain inflammation in the aftermath of TBI. |
| format | Article |
| id | doaj-art-10a8be98210142498103d4b72f76d365 |
| institution | OA Journals |
| issn | 1476-9255 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
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| series | Journal of Inflammation |
| spelling | doaj-art-10a8be98210142498103d4b72f76d3652025-08-20T01:57:25ZengBMCJournal of Inflammation1476-92552025-03-0122111610.1186/s12950-025-00439-9Contribution of brain pericytes to neuroinflammation following repetitive head traumaArianna Cembran0Maxwell Eisenbaum1Daniel Paris2Michael Mullan3Fiona Crawford4Scott Ferguson5Corbin Bachmeier6The Roskamp InstituteThe Roskamp InstituteThe Roskamp InstituteThe Roskamp InstituteThe Roskamp InstituteThe Roskamp InstituteThe Roskamp InstituteAbstract 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 cell viability, indicating that cytokine treatment did not induce cytotoxicity. Further, elevated levels of pro-inflammatory markers STAT1 and p-NFkB were observed in response to cytokine exposure, with a concurrent increase in VCAM1 and MMP9 expression. PDGF-BB treatment significantly attenuated the inflammatory response in pericytes, reducing PDGFRβ levels and the activation of inflammatory pathways, including STAT1 and NFkB. Cytokine secretion profiles also revealed that PDGF-BB, when administered post-inflammatory insult, selectively reduced pro-inflammatory cytokines such as IL-1β and IFN-γ. Additionally, phenytoin treatment in r-mTBI mice decreased IL-1β, TNF-α, IL-5, and KC/GRO levels in isolated brain pericytes, while IL-2, IL-4, and IL-6 levels were unchanged compared to untreated r-mTBI animals. Conclusions Our results indicate an immunoreactive role for brain pericytes in the propagation of neuroinflammation. Moreover, following brain insults, we found PDGF-BB stimulation can normalize pericyte function and reduce cerebrovascular inflammation, a key factor in secondary brain injury. Targeting brain pericytes may provide novel therapeutic opportunities to improve cerebrovascular health and reduce brain inflammation in the aftermath of TBI.https://doi.org/10.1186/s12950-025-00439-9TBINeuroinflammationBlood-brain barrierBrain pericytesCytokinesPDGF-BB |
| spellingShingle | Arianna Cembran Maxwell Eisenbaum Daniel Paris Michael Mullan Fiona Crawford Scott Ferguson Corbin Bachmeier Contribution of brain pericytes to neuroinflammation following repetitive head trauma Journal of Inflammation TBI Neuroinflammation Blood-brain barrier Brain pericytes Cytokines PDGF-BB |
| title | Contribution of brain pericytes to neuroinflammation following repetitive head trauma |
| title_full | Contribution of brain pericytes to neuroinflammation following repetitive head trauma |
| title_fullStr | Contribution of brain pericytes to neuroinflammation following repetitive head trauma |
| title_full_unstemmed | Contribution of brain pericytes to neuroinflammation following repetitive head trauma |
| title_short | Contribution of brain pericytes to neuroinflammation following repetitive head trauma |
| title_sort | contribution of brain pericytes to neuroinflammation following repetitive head trauma |
| topic | TBI Neuroinflammation Blood-brain barrier Brain pericytes Cytokines PDGF-BB |
| url | https://doi.org/10.1186/s12950-025-00439-9 |
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