Impaired capillary-venous drainage contributes to gliosis and demyelination in white matter during aging

作者：Stefan Stamenković, Franca Schmid, Gökçe Gürler, Farzaneh Abolmaali, Nicolas A. Weitermann, Kevin Takasaki, Stephanie Bonney, Maria J. Sosa, Hannah Bennett, Yongsoo Kim, Jack Waters, Andy Y. Shih · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2024 · DOI：10.1101/2024.02.11.579849 · 被引用次数：12 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Neurological Disease Mechanisms and Treatments、Barrier Structure and Function Studies

The progressive loss of cerebral white matter during aging contributes to cognitive decline, but whether reduced blood flow is a cause or consequence remains debated. Using deep multi-photon imaging in mice, we examined microvascular networks perfusing myelinated tissues in cortical layer 6 and corpus callosum. We identified sparse, wide-reaching venules, termed principal cortical venules, that exclusively drain deep tissues and resemble vasculature at the human cortex and U-fiber interface. Aging involved selective constriction and rarefaction of capillaries in deep branches of principal cortical venules. This resulted in mild hypoperfusion that was associated with microgliosis, astrogliosis and demyelination in deep tissues, but not upper cortex. Inducing a comparable hypoperfusion in adult mice using carotid artery stenosis triggered a similar tissue pathology specific to layer 6 and corpus callosum. Thus, impaired capillary-venous drainage is a contributor to hypoperfusion and a potential therapeutic target for preserving blood flow to white matter during aging.