Exploring immune-endothelial interactions in neuroinflammation and vascular dysfunction

Neuroinflammation and cerebrovascular endothelial dysfunction are traditionally studied as parallel processes confined to individual disease categories. Yet a growing body of evidence indicates that they operate as components of a tightly coupled, self-amplifying circuit: the immune-endothelial-neural axis. Within this axis, the peripheral immune system, cerebrovascular endothelium, and neural networks continuously modulate one another across disease contexts. This Review summarizes current knowledge on the bidirectional immune-endothelial interactions that underlie blood-brain barrier disruption and neuroinflammation across cerebrovascular disorders, neuroimmune diseases, and neurodegenerative conditions. A systems-level comparison across disease categories identifies shared pathological hallmarks alongside disease-specific signatures of tempo, vascular scale, and regional vulnerability. Emerging therapeutic strategies are considered along the three limbs of the axis: immunomodulation, endothelial protection and barrier stabilization, and neural recovery, including traditional Chinese medicine as a multitarget approach. By framing neurological disorders through the immune-endothelial-neural axis, this Review proposes a unifying framework that bridges disease boundaries and identifies common mechanistic targets for future translational research. The framework is offered as a testable proposition in which the relative contribution of each limb differs between disorders.