Oxidative stress and inflammatory signaling in hypertensive stroke: mechanistic integration in vascular and...

Hypertensive stroke emerges through complex interactions between oxidative stress, inflammatory signaling, vascular remodeling, and neurovascular dysfunction; however, the mechanisms coordinating these processes across vascular and neurovascular compartments remain incompletely resolved. This review integrates current mechanistic evidence to clarify how compartment-specific redox imbalance interfaces with inflammatory signaling to drive endothelial dysfunction, extracellular matrix remodeling, arterial stiffening, microvascular rarefaction, and neurovascular unit instability. Reactive oxygen species (ROS) derived from NADPH oxidases and mitochondrial electron transport systems act as spatially restricted signaling mediators that influence key regulatory pathways, including PI3K/Akt, NF-κB, and Nrf2. NOX2-associated ROS signaling appears to contribute predominantly to endothelial inflammatory amplification, nitric oxide depletion, leukocyte recruitment, and blood-brain barrier destabilization, whereas NOX4-related activity is more strongly linked to vascular stiffening, extracellular matrix reorganization, and chronic fibrotic remodeling. Inflammatory signaling evolves through pulsatile and region-specific activation patterns rather than uniform progression, while incomplete antioxidant compensation sustains persistent low-grade oxidative and inflammatory signaling. The neurovascular unit emerges as a major convergence site where endothelial dysfunction, glial activation, mitochondrial instability, and neuronal metabolic vulnerability progressively interact under chronic stress conditions. Despite substantial mechanistic progress, major translational limitations remain, including insufficient spatial and temporal resolution of current biomarker strategies and limited integration of compartment-specific signaling dynamics. Future progress will likely depend on spatially resolved analytical platforms, standardized mechanistic frameworks, and integrative systems-level models capable of linking localized molecular signaling with clinically interpretable vascular outcomes in hypertensive stroke.