Inflammation in Brain Endothelial Cells Driven by TNF-STAT3 Signaling Axis

Researchers at Vanderbilt University have found that tumor necrosis factor (TNF) triggers inflammation in brain endothelial cells through a TNF-STAT3 signaling axis, leading to blood-brain barrier dysfunction. This discovery highlights the critical role of astrocytes in blood-brain barrier function and the potential therapeutic implications of targeting the TNF-STAT3-alpha 1ACT pathway. By examining the role of astrocytes in blood-brain barrier function using an iPSC-derived cell co-culture model, the study shed light on the molecular mechanisms underlying neurodegenerative conditions and aging.

Key Takeaways:

• Astrocytes play a crucial role in blood-brain barrier function and may be critical in understanding neurodegenerative conditions.
• Tumor necrosis factor (TNF) triggers inflammation in brain endothelial cells through a TNF-STAT3 signaling axis.
• The TNF-STAT3-alpha 1ACT pathway is involved in blood-brain barrier dysfunction.
• Astrocytic STAT3 activation is correlated with vascular inflammation in postmortem human tissue.
• In murine brain organotypic cultures, astrocyte-specific silencing of Serpina3n reduced vascular inflammation after TNF challenge.
• Treatment with recombinant Serpina3n in both ex vivo explant cultures and in vivo was sufficient to induce BBB dysfunction-related molecular changes.
• This study provides evidence for the TNF-STAT3-alpha 1ACT signaling axis as a driver of an inflammatory reactive astrocyte signature contributing to BBB dysfunction.

Statistics:

• The study used an iPSC-derived cell co-culture model to examine the role of astrocytes in blood-brain barrier function.
• The research included data from postmortem human tissue and murine brain organotypic cultures.
• The study involved a tumour necrosis factor (TNF) challenge.
• 9 figures and 2 tables were presented in the study.
• The research was supported by the U.S. Department of Health & Human Services | National Institutes of Health, the Chan Zuckerberg Initiative.

Sources:

• NewsRx. New Tumor Necrosis Factors Study Findings Recently Were Reported by Researchers at Vanderbilt University (Reactive Astrocytes Transduce Inflammation In a Blood-brain Barrier Model Through a Tnf-stat3 Signaling Axis and Secretion of Alpha ...). Health & Medicine Week. December 9, 2022; p 4119.
• Nature Communications. Reactive Astrocytes Transduce Inflammation In a Blood-brain Barrier Model Through a Tnf-stat3 Signaling Axis and Secretion of Alpha 1-antichymotrypsin. 2022;13(1).
• Nature Publishing Group. www.nature.com/.
• Nature Communications. www.nature.com/ncomms/.