Age-related ultrastructural neurovascular changes in the female mouse cortex and hippocampus

Frias Anaya, Eduardo; Gromnicova, Radka; Kraev, Igor; Rogachevsky, Vadim; Male, David; Crea, Francesco; Hawkes, Cheryl and Romero, Ignacio A. (2021). Age-related ultrastructural neurovascular changes in the female mouse cortex and hippocampus. Neurobiology of Aging, 101 pp. 273–284.



Blood-Brain Barrier (BBB) breakdown occurs in ageing and neurodegenerative diseases. Although age-associated alterations have previously been described, most studies focused in male brains; hence, little is known about BBB breakdown in females. This study measured ultrastructural features in the ageing female BBB using transmission electron microscopy (TEM) and 3D reconstruction of cortical and hippocampal capillaries from 6- and 24-month-old female C57BL/6J mice. Aged cortical capillaries showed more changes than hippocampal capillaries. Specifically, aged cortex showed thicker basement membrane (BM), higher number and volume of endothelial pseudopods, decreased endothelial mitochondrial number, larger pericyte mitochondria, higher pericyte – endothelial cell contact and increased tight junction tortuosity compared to young animals. Only increased BM thickness and pericyte mitochondrial volume were observed in aged hippocampus. Regional comparison revealed significant differences in endothelial pseudopods and tight junctions between cortex and hippocampus of 24-month-old mice. Therefore, the ageing female BBB shows region-specific ultrastructural alterations that may lead to oxidative stress and abnormal capillary blood flow and barrier stability, potentially contributing to cerebrovascular diseases, particularly in post-menopausal women.

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