Impaired capillary-venous drainage contributes to gliosis and demyelination in white matter during aging
Year: 2024
Type: preprint
Abstract: 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.
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Brain Drain: In Vivo Optical Interrogation of Venular Function in Gray and White Matter, Energy Supply in Whole Brain Microvascular Networks in Health and Disease – Quantifying the Relevance of Small-Scale Disturbances, Optical Interrogation of Venular Function in Cerebral Gray and White Matter, Pericyte control of capillary perfusion in the Alzheimer's disease brain, Medical Scientist Training Program
OpenAlex ID: W4391743555