Diagnostics and rehabilitation of post-stroke visual field loss using innovative visual field evaluation. The impact of losing driving privileges (DRIVE-study): Protocol for a randomized controlled tr

Brain endothelial cells (ECs) play a crucial role in maintaining the integrity of the blood-brain barrier (BBB), serving as a selective interface that separates the brain from systemic circulation . ECs are also key components of the neurovascular unit, working in close association with the extracellular matrix, pericytes (PCs), astrocytes, and neurons to regulate brain homeostasis . Aging is related to impairing this unit, resulting in a reduced capacity to maintain stem cell and neuronal function, decreased cerebral blood flow, and increased toxic leakage , , . Aging has also been strongly related to EC senescence, leading to functional deterioration of the BBB , . Senescent ECs exhibit increased expression of inflammatory signaling pathways [e.g., nuclear factor κ B, interleukin 6 , and intercellular adhesion molecule 1 ], enhanced interactions with circulating immune cells [e.g., macrophages ], disruption of tight junction proteins [e.g., claudin-5 and occludin ], and impaired transcellular transport systems, including reductions in glucose transporter 1 (GLUT1) and P-glycoprotein function , . Together, these alterations contribute to BBB dysfunction and increased vulnerability of the aging brain to neurodegenerative processes. The brain vasculature is highly heterogeneous, consisting of veins and venules, arteries and arterioles, and capillaries, each with unique molecular signatures and specialized functions . Currently, advances in single-RNA sequencing (scRNA-seq) have made it possible to explore cellular heterogeneity in the brain ECs, revealing distinct gene expression profiles for EC subtypes in disease models such as autoimmune encephalomyelitis, multiple sclerosis, vascular diseases, hypertrophic scars, pulmonary arterial hypertension, and obesity , , , , . Recent scRNA-seq studies have revealed that brain ECs show segment-specific gene expression patterns, with venous, arterial, and capillary ECs each playing different molecular roles. Among these, hippocampal capillary ECs appear particularly sensitive to aging, exhibiting pronounced transcriptional changes such as increased gene expression involved in oxidative stress responses (, ) and innate immunity (e.g., , ) , , . By contrast, arterial and venous ECs show more modest transcriptional changes, with fewer differentially expressed genes (DEGs) related to these pathways, highlighting the unique vulnerability of capillary ECs to age-related molecular alterations . Aging induces zonation-dependent transcriptomic changes in ECs, particularly in capillaries, affecting BBB integrity, energy metabolism, and immune signaling, some of which are associated with Alzheimer's disease (AD) risk genes and are pharmacologically reversible . In addition, ECs display regional heterogeneity across the CNS, with specialized genes such as regulating local retinoid deposition and influencing the function of specific neural circuits .