Stress-induced regional characteristics of the blood-brain barrier

The blood-brain barrier (BBB) is a neurovascular unit composed of brain microvascular endothelial cells, astrocytes, pericytes, and the basement membrane, playing a critical role in maintaining brain microenvironment homeostasis. However, exposure to external stressors can disrupt the structure and function of the BBB, leading to microenvironmental imbalances and the onset of various neurological disorders. Notably, the impact of stress on the BBB exhibits significant regional heterogeneity across different brain regions, influenced by factors such as the structural and functional characteristics of brain regions, modalities and duration of stress, and sex differences. In recent years, advancements in high-throughput technologies, including single-cell RNA sequencing and spatial transcriptomics, have gradually revealed the molecular features underlying the regional heterogeneity of the BBB under various stress conditions. This review provides a comprehensive overview of the structure and function of the BBB, elaborates the role of BBB in the progression and treatment of neurological disorders, summarizes recent research on stress-induced regional heterogeneity in BBB alterations, and integrates potential contributing factors and the underlying mechanisms. Besides, this review outlines the current applications of new technologies in BBB heterogeneity-related research and the potential values of BBB heterogeneity in clinical therapy, offering new insights and strategies for the diagnosis and treatment of neurological disorders.