How do pro-inflammatory cytokines alter miRNA profiles in brain endothelial cells? Mechanisms, consequences, and therapeutic strategies for blood-brain barrier protection

The blood-brain barrier (BBB) is a critical interface between the systemic circulation and the central nervous system, and its integrity is essential for maintaining brain homeostasis. During neuroinflammation and infection, pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interferon gamma (IFN-γ) profoundly alter the molecular landscape of brain endothelial cells, including their microRNA (miRNA) expression profiles. This review synthesizes current evidence demonstrating that TNF-α and IFN-γ induce specific miRNA changes in human brain endothelial cells, thereby regulating tight junction proteins, adhesion molecules, and inflammatory signaling pathways. These cytokine-induced miRNA alterations contribute to BBB dysfunction through multiple mechanisms, including disruption of junctional complexes, increased leukocyte adhesion and transmigration, and activation of pro-inflammatory cascades. Understanding these miRNA-mediated regulatory networks offers potential therapeutic targets for preserving BBB integrity during infectious diseases, with emerging evidence from cerebral malaria highlighting the translational potential of miRNA-based interventions.